Skip to main content
PMC home page
Cellular & Molecular Biology Letters logoLink to Cellular & Molecular Biology Letters
. 2014 Feb 25;19(1):158–179. doi: 10.2478/s11658-014-0185-5

Spectrin and phospholipids — the current picture of their fascinating interplay

Dżamila M Bogusławska 1, Beata Machnicka 1, Anita Hryniewicz-Jankowska 2, Aleksander Czogalla 2,3,4,✉
PMCID: PMC6276000  PMID: 24569979

Abstract

The spectrin-based membrane skeleton is crucial for the mechanical stability and resilience of erythrocytes. It mainly contributes to membrane integrity, protein organization and trafficking. Two transmembrane protein macro-complexes that are linked together by spectrin tetramers play a crucial role in attaching the membrane skeleton to the cell membrane, but they are not exclusive. Considerable experimental data have shown that direct interactions between spectrin and membrane lipids are important for cell membrane cohesion. Spectrin is a multidomain, multifunctional protein with several distinctive structural regions, including lipid-binding sites within CH tandem domains, a PH domain, and triple helical segments, which are excellent examples of ligand specificity hidden in a regular repetitive structure, as recently shown for the ankyrin-sensitive lipid-binding domain of beta spectrin. In this review, we summarize the state of knowledge about interactions between spectrin and membrane lipids.

Keywords: Spectrin-phospholipid interactions, Spectrin repeats, Spectrin tetramers, Ankyrin, Erythrocytes, Actin-binding domain, Pleckstrin homology domain, Dystrophin, Lipid bilayer, Membrane skeleton

Full Text

The Full Text of this article is available as a PDF (1.9 MB).

Abbreviations used

ABD

actin-binding domain

AE1

anion exchanger 1

Ank

ankyrin

CH

calponin homology domain

GPC

glycophorin C

MPP1

membrane palmitoylated protein 1

PC

phosphatidylcholine

PE

phosphatidylethanolamine

PH

pleckstrin homology domain

PI

phosphatidylinositol

PI(4,5)P2

phosphatidylinositol-4,5-bisphosphate

PS

phosphatidylserine

SH3

SRC homology 3 domain

UPA

Unc5-PIDD-ankyrin domain

ZU5

domain present in ZO-1 and Unc5-like netrin receptors

References

  • 1.Marchesi VT, Steers E., Jr. Selective solubilization of a protein component of the red cell membrane. Science. 1968;159:203–204. doi: 10.1126/science.159.3811.203. [DOI] [PubMed] [Google Scholar]
  • 2.Sahr KE, Laurila P, Kotula L, Scarpa AL, Coupal E, Leto TL, Linnenbach AJ, Winkelmann JC, Speicher DW, Marchesi VT, Curtis PJ, Forget BG. The complete cDNA and polypeptide sequences of human erythroid alpha-spectrin. J. Biol. Chem. 1990;265:4434–4443. [PubMed] [Google Scholar]
  • 3.Winkelmann JC, Chang JG, Tse WT, Scarpa AL, Marchesi VT, Forget BG. Full-length sequence of the cDNA for human erythroid beta-spectrin. J. Biol. Chem. 1990;265:11827–11832. [PubMed] [Google Scholar]
  • 4.Sevinc A, Witek MA, Fung LW. Yeast two-hybrid and itc studies of alpha and beta spectrin interaction at the tetramerization site. Cell. Mol. Biol. Lett. 2011;16:452–461. doi: 10.2478/s11658-011-0017-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Speicher DW, Marchesi VT. Erythrocyte spectrin is comprised of many homologous triple helical segments. Nature. 1984;311:177–180. doi: 10.1038/311177a0. [DOI] [PubMed] [Google Scholar]
  • 6.Sevinc A, Fung LW. Non-erythroid beta spectrin interacting proteins and their effects on spectrin tetramerization. Cell. Mol. Biol. Lett. 2011;16:595–609. doi: 10.2478/s11658-011-0025-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Byers TJ, Branton D. Visualization of the protein associations in the erythrocyte membrane skeleton. Proc. Natl. Acad. Sci. U S A. 1985;82:6153–6157. doi: 10.1073/pnas.82.18.6153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Liu SC, Derick LH, Palek J. Visualization of the hexagonal lattice in the erythrocyte membrane skeleton. J. Cell Biol. 1987;104:527–536. doi: 10.1083/jcb.104.3.527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Swihart AH, Mikrut JM, Ketterson JB, Macdonald RC. Atomic force microscopy of the erythrocyte membrane skeleton. J. Microsc. 2001;204:212–225. doi: 10.1046/j.1365-2818.2001.00960.x. [DOI] [PubMed] [Google Scholar]
  • 10.Nans A, Mohandas N, Stokes DL. Native ultrastructure of the red cell cytoskeleton by cryo-electron tomography. Biophys. J. 2011;101:2341–2350. doi: 10.1016/j.bpj.2011.09.050. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Ursitti JA, Kotula L, DeSilva TM, Curtis PJ, Speicher DW. Mapping the human erythrocyte beta-spectrin dimer initiation site using recombinant peptides and correlation of its phasing with the alpha-actinin dimer site. J. Biol. Chem. 1996;271:6636–6644. doi: 10.1074/jbc.271.12.6636. [DOI] [PubMed] [Google Scholar]
  • 12.Morrow JS, Marchesi VT. Self-assembly of spectrin oligomers in vitro: a basis for a dynamic cytoskeleton. J. Cell Biol. 1981;88:463–468. doi: 10.1083/jcb.88.2.463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Machnicka B, Czogalla A, Hryniewicz-Jankowska A, Boguslawska DM, Grochowalska R, Heger E, Sikorski AF. Spectrins: A structural platform for stabilization and activation of membrane channels, receptors and transporters. Biochim. Biophys. Acta. 2014;1838:620–634. doi: 10.1016/j.bbamem.2013.05.002. [DOI] [PubMed] [Google Scholar]
  • 14.De Matteis MA, Morrow JS. Spectrin tethers and mesh in the biosynthetic pathway. J. Cell Sci. 2000;113:2331–2343. doi: 10.1242/jcs.113.13.2331. [DOI] [PubMed] [Google Scholar]
  • 15.Machnicka B, Grochowalska R, Boguslawska DM, Sikorski AF, Lecomte MC. Spectrin-based skeleton as an actor in cell signaling. Cell. Mol. Life Sci. 2012;69:191–201. doi: 10.1007/s00018-011-0804-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Yan Y, Winograd E, Viel A, Cronin T, Harrison SC, Branton D. Crystal structure of the repetitive segments of spectrin. Science. 1993;262:2027–2030. doi: 10.1126/science.8266097. [DOI] [PubMed] [Google Scholar]
  • 17.Kotula L, DeSilva TM, Speicher DW, Curtis PJ. Functional characterization of recombinant human red cell alpha-spectrin polypeptides containing the tetramer binding site. J. Biol. Chem. 1993;268:14788–14793. [PubMed] [Google Scholar]
  • 18.Wasenius VM, Saraste M, Salven P, Eramaa M, Holm L, Lehto VP. Primary structure of the brain alpha-spectrin. J. Cell Biol. 1989;108:79–93. doi: 10.1083/jcb.108.1.79. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Pawson T. Protein modules and signalling networks. Nature. 1995;373:573–580. doi: 10.1038/373573a0. [DOI] [PubMed] [Google Scholar]
  • 20.Musacchio A, Noble M, Pauptit R, Wierenga R, Saraste M. Crystal structure of a Src-homology 3 (SH3) domain. Nature. 1992;359:851–855. doi: 10.1038/359851a0. [DOI] [PubMed] [Google Scholar]
  • 21.Rotter B, Kroviarski Y, Nicolas G, Dhermy D, Lecomte MC. AlphaII-spectrin is an in vitro target for caspase-2, and its cleavage is regulated by calmodulin binding. Biochem. J. 2004;378:161–168. doi: 10.1042/BJ20030955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Glantz SB, Cianci CD, Iyer R, Pradhan D, Wang KK, Morrow JS. Sequential degradation of alphaII and betaII spectrin by calpain in glutamate or maitotoxin-stimulated cells. Biochemistry. 2007;46:502–513. doi: 10.1021/bi061504y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Harris AS, Croall DE, Morrow JS. The calmodulin-binding site in alpha-fodrin is near the calcium-dependent protease-I cleavage site. J. Biol. Chem. 1988;263:15754–15761. [PubMed] [Google Scholar]
  • 24.Harris AS, Morrow JS. Proteolytic processing of human brain alpha spectrin (fodrin): identification of a hypersensitive site. J. Neurosci. 1988;8:2640–2651. doi: 10.1523/JNEUROSCI.08-07-02640.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Harris AS, Morrow JS. Calmodulin and calcium-dependent protease I coordinately regulate the interaction of fodrin with actin. Proc. Natl. Acad. Sci. USA. 1990;87:3009–3013. doi: 10.1073/pnas.87.8.3009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Nicolas G, Fournier CM, Galand C, Malbert-Colas L, Bournier O, Kroviarski Y, Bourgeois M, Camonis JH, Dhermy D, Grandchamp B, Lecomte MC. Tyrosine phosphorylation regulates alpha II spectrin cleavage by calpain. Mol. Cell. Biol. 2002;22:3527–3536. doi: 10.1128/MCB.22.10.3527-3536.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Nedrelow JH, Cianci CD, Morrow JS. c-Src binds alpha II spectrin’s Src homology 3 (SH3) domain and blocks calpain susceptibility by phosphorylating Tyr1176. J. Biol. Chem. 2003;278:7735–7741. doi: 10.1074/jbc.M210988200. [DOI] [PubMed] [Google Scholar]
  • 28.Buevich AV, Lundberg S, Sethson I, Edlund U, Backman L. NMR studies of calcium-binding to mutant alpha-spectrin EF-hands. Cell. Mol. Biol. Lett. 2004;9:167–186. [PubMed] [Google Scholar]
  • 29.Feng YD, Li J, Zhou WC, Jia ZG, Wei Q. Identification of the critical structural determinants of the EF-hand domain arrangements in calcium binding proteins. Biochim. Biophys. Acta. 2012;1824:608–619. doi: 10.1016/j.bbapap.2012.01.005. [DOI] [PubMed] [Google Scholar]
  • 30.Lundberg S, Buevich AV, Sethson I, Edlund U, Backman L. Calcium-binding mechanism of human non-erythroid alpha-spectrin EFstructures. Biochemistry. 1997;36:7199–7208. doi: 10.1021/bi9631531. [DOI] [PubMed] [Google Scholar]
  • 31.Trave G, Lacombe PJ, Pfuhl M, Saraste M, Pastore A. Molecular mechanism of the calcium-induced conformational change in the spectrin EF-hands. EMBO J. 1995;14:4922–4931. doi: 10.1002/j.1460-2075.1995.tb00175.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Nestor MW, Cai X, Stone MR, Bloch RJ, Thompson SM. The actin-binding domain of betaI-spectrin regulates the morphological and functional dynamics of dendritic spines. PLoS One. 2011;6:e16197. doi: 10.1371/journal.pone.0016197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Karinch AM, Zimmer WE, Goodman SR. The identification and sequence of the actin-binding domain of human red blood cell beta-spectrin. J. Biol. Chem. 1990;265:11833–11840. [PubMed] [Google Scholar]
  • 34.Macias MJ, Musacchio A, Ponstingl H, Nilges M, Saraste M, Oschkinat H. Structure of the pleckstrin homology domain from betaspectrin. Nature. 1994;369:675–677. doi: 10.1038/369675a0. [DOI] [PubMed] [Google Scholar]
  • 35.Zhang P, Talluri S, Deng H, Branton D, Wagner G. Solution structure of the pleckstrin homology domain of Drosophila beta-spectrin. Structure. 1995;3:1185–1195. doi: 10.1016/s0969-2126(01)00254-4. [DOI] [PubMed] [Google Scholar]
  • 36.Zhang P, Sridharan D, Lambert MW. Knockdown of mu-calpain in Fanconi anemia, FA-A, cells by siRNA restores alphaII spectrin levels and corrects chromosomal instability and defective DNA interstrand cross-link repair. Biochemistry. 2010;49:5570–5581. doi: 10.1021/bi100656j. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Bennett V, Stenbuck PJ. Identification and partial purification of ankyrin, the high affinity membrane attachment site for human erythrocyte spectrin. J. Biol. Chem. 1979;254:2533–2541. [PubMed] [Google Scholar]
  • 38.Bennett V, Healy J. Organizing the fluid membrane bilayer: diseases linked to spectrin and ankyrin. Trends Mol. Med. 2008;14:28–36. doi: 10.1016/j.molmed.2007.11.005. [DOI] [PubMed] [Google Scholar]
  • 39.Luna EJ, Kidd GH, Branton D. Identification by peptide analysis of the spectrin-binding protein in human erythrocytes. J. Biol. Chem. 1979;254:2526–2532. [PubMed] [Google Scholar]
  • 40.Yu J, Goodman SR. Syndeins: the spectrin-binding protein(s) of the human erythrocyte membrane. Proc. Natl. Acad. Sci. USA. 1979;76:2340–2344. doi: 10.1073/pnas.76.5.2340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Ipsaro JJ, Harper SL, Messick TE, Marmorstein R, Mondragon A, Speicher DW. Crystal structure and functional interpretation of the erythrocyte spectrin tetramerization domain complex. Blood. 2010;115:4843–4852. doi: 10.1182/blood-2010-01-261396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.La-Borde PJ, Stabach PR, Simonovic I, Morrow JS, Simonovic M. Ankyrin recognizes both surface character and shape of the 14–15 di-repeat of beta-spectrin. Biochem. Biophys. Res. Commun. 2010;392:490–494. doi: 10.1016/j.bbrc.2010.01.046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Kolondra A, Grzybek M, Chorzalska A, Sikorski AF. The 22.5 kDa spectrin-binding domain of ankyrinR binds spectrin with high affinity and changes the spectrin distribution in cells in vivo. Protein Expr. Purif. 2008;60:157–164. doi: 10.1016/j.pep.2008.04.002. [DOI] [PubMed] [Google Scholar]
  • 44.Lu PW, Soong CJ, Tao M. Phosphorylation of ankyrin decreases its affinity for spectrin tetramer. J. Biol. Chem. 1985;260:14958–14964. [PubMed] [Google Scholar]
  • 45.Kolondra A, Lenoir M, Wolny M, Czogalla A, Overduin M, Sikorski AF, Grzybek M. The role of hydrophobic interactions in ankyrin-spectrin complex formation. Biochim. Biophys. Acta. 2010;1798:2084–2089. doi: 10.1016/j.bbamem.2010.07.024. [DOI] [PubMed] [Google Scholar]
  • 46.Yasunaga M, Ipsaro JJ, Mondragon A. Structurally similar but functionally diverse ZU5 domains in human erythrocyte ankyrin. J. Mol. Biol. 2012;417:336–350. doi: 10.1016/j.jmb.2012.01.041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Czogalla A, Sikorski AF. Do we already know how spectrin attracts ankyrin? Cell. Mol. Life Sci. 2010;67:2679–2683. doi: 10.1007/s00018-010-0371-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48.Bennett V, Baines AJ. Spectrin and ankyrin-based pathways: metazoan inventions for integrating cells into tissues. Physiol. Rev. 2001;81:1353–1392. doi: 10.1152/physrev.2001.81.3.1353. [DOI] [PubMed] [Google Scholar]
  • 49.Stefanovic M, Markham NO, Parry EM, Garrett-Beal LJ, Cline AP, Gallagher PG, Low PS, Bodine DM. An 11-amino acid betahairpin loop in the cytoplasmic domain of band 3 is responsible for ankyrin binding in mouse erythrocytes. Proc. Natl. Acad. Sci. USA. 2007;104:13972–13977. doi: 10.1073/pnas.0706266104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Kim S, Brandon S, Zhou Z, Cobb CE, Edwards SJ, Moth CW, Parry CS, Smith JA, Lybrand TP, Hustedt EJ, Beth AH. Determination of structural models of the complex between the cytoplasmic domain of erythrocyte band 3 and ankyrin-R repeats 13–24. J. Biol. Chem. 2011;286:20746–20757. doi: 10.1074/jbc.M111.230326. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51.Nicolas V, Le Van Kim C, Gane P, Birkenmeier C, Cartron JP, Colin Y, Mouro-Chanteloup I. Rh-RhAG/ankyrin-R, a new interaction site between the membrane bilayer and the red cell skeleton, is impaired by Rh(null)-associated mutation. J. Biol. Chem. 2003;278:25526–25533. doi: 10.1074/jbc.M302816200. [DOI] [PubMed] [Google Scholar]
  • 52.Bruce LJ, Beckmann R, Ribeiro ML, Peters LL, Chasis JA, Delaunay J, Mohandas N, Anstee DJ, Tanner MJ. A band 3-based macrocomplex of integral and peripheral proteins in the RBC membrane. Blood. 2003;101:4180–4188. doi: 10.1182/blood-2002-09-2824. [DOI] [PubMed] [Google Scholar]
  • 53.Franco T, Low PS. Erythrocyte adducin: a structural regulator of the red blood cell membrane. Transfus. Clin. Biol. 2010;17:87–94. doi: 10.1016/j.tracli.2010.05.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Gauthier E, Guo X, Mohandas N, An X. Phosphorylationdependent perturbations of the 4.1R-associated multiprotein complex of the erythrocyte membrane. Biochemistry. 2011;50:4561–4567. doi: 10.1021/bi200154g. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 55.Khan AA, Hanada T, Mohseni M, Jeong JJ, Zeng L, Gaetani M, Li D, Reed BC, Speicher DW, Chishti AH. Dematin and adducin provide a novel link between the spectrin cytoskeleton and human erythrocyte membrane by directly interacting with glucose transporter-1. J. Biol. Chem. 2008;283:14600–14609. doi: 10.1074/jbc.M707818200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Salomao M, Zhang X, Yang Y, Lee S, Hartwig JH, Chasis JA, Mohandas N, An X. Protein 4.1R-dependent multiprotein complex: new insights into the structural organization of the red blood cell membrane. Proc. Natl. Acad. Sci. U S A. 2008;105:8026–8031. doi: 10.1073/pnas.0803225105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57.Nunomura W, Takakuwa Y, Parra M, Conboy J, Mohandas N. Regulation of protein 4.1R, p55, and glycophorin C ternary complex in human erythrocyte membrane. J. Biol. Chem. 2000;275:24540–24546. doi: 10.1074/jbc.M002492200. [DOI] [PubMed] [Google Scholar]
  • 58.Chishti AH, Kim AC, Marfatia SM, Lutchman M, Hanspal M, Jindal H, Liu SC, Low PS, Rouleau GA, Mohandas N, Chasis JA, Conboy JG, Gascard P, Takakuwa Y, Huang SC, Benz EJ, Jr, Bretscher A, Fehon RG, Gusella JF, Ramesh V, Solomon F, Marchesi VT, Tsukita S, Tsukita S, Arpin M, Louvard D, Tonks NK, Anderson JM, Fanning AS, Bryant PJ, Woods DF, Hoover KB. The FERM domain: a unique module involved in the linkage of cytoplasmic proteins to the membrane. Trends Biochem. Sci. 1998;23:281–282. doi: 10.1016/s0968-0004(98)01237-7. [DOI] [PubMed] [Google Scholar]
  • 59.Diakowski W, Grzybek M, Sikorski AF. Protein 4.1, a component of the erythrocyte membrane skeleton and its related homologue proteins forming the protein 4.1/FERM superfamily. Folia Histochem. Cytobiol. 2006;44:231–248. [PubMed] [Google Scholar]
  • 60.Koshino I, Mohandas N, Takakuwa Y. Identification of a novel role for dematin in regulating red cell membrane function by modulating spectrin-actin interaction. J. Biol. Chem. 2012;287:35244–35250. doi: 10.1074/jbc.M111.305441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 61.Korsgren C, Peters LL, Lux SE. Protein 4.2 binds to the carboxylterminal EF-hands of erythroid alpha-spectrin in a calcium- and calmodulin-dependent manner. J. Biol. Chem. 2010;285:4757–4770. doi: 10.1074/jbc.M109.056200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 62.Delaunay J. The molecular basis of hereditary red cell membrane disorders. Blood Rev. 2007;21:1–20. doi: 10.1016/j.blre.2006.03.005. [DOI] [PubMed] [Google Scholar]
  • 63.Boguslawska DM, Heger E, Sikorski AF. [Molecular mechanism of hereditary spherocytosis] Pol. Merkur. Lekarski. 2006;20:112–116. [PubMed] [Google Scholar]
  • 64.Barcellini W, Bianchi P, Fermo E, Imperiali FG, Marcello AP, Vercellati C, Zaninoni A, Zanella A. Hereditary red cell membrane defects: diagnostic and clinical aspects. Blood Transfus. 2011;9:274–277. doi: 10.2450/2011.0086-10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 65.An X, Mohandas N. Disorders of red cell membrane. Br. J. Haematol. 2008;141:367–375. doi: 10.1111/j.1365-2141.2008.07091.x. [DOI] [PubMed] [Google Scholar]
  • 66.Mombers C, de Gier J, Demel RA, van Deenen LL. Spectrin-phospholipid interaction. A monolayer study. Biochim. Biophys. Acta. 1980;603:52–62. doi: 10.1016/0005-2736(80)90390-9. [DOI] [PubMed] [Google Scholar]
  • 67.Haest CW. Interactions between membrane skeleton proteins and the intrinsic domain of the erythrocyte membrane. Biochim. Biophys. Acta. 1982;694:331–352. doi: 10.1016/0304-4157(82)90001-6. [DOI] [PubMed] [Google Scholar]
  • 68.Sikorski AF, Hanus-Lorenz B, Jezierski A, Dluzewski AR. Interaction of membrane skeletal proteins with membrane lipid domain. Acta Biochim. Pol. 2000;47:565–578. [PubMed] [Google Scholar]
  • 69.Isenberg H, Kenna JG, Green NM, Gratzer WB. Binding of hydrophobic ligands to spectrin. FEBS Lett. 1981;129:109–112. doi: 10.1016/0014-5793(81)80767-3. [DOI] [PubMed] [Google Scholar]
  • 70.Kahana E, Pinder JC, Smith KS, Gratzer WB. Fluorescence quenching of spectrin and other red cell membrane cytoskeletal proteins. Relation to hydrophobic binding sites. Biochem. J. 1992;282:75–80. doi: 10.1042/bj2820075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 71.Bitbol M, Dempsey C, Watts A, Devaux PF. Weak interaction of spectrin with phosphatidylcholine-phosphatidylserine multilayers: a 2H and 31P NMR study. FEBS Lett. 1989;244:217–222. doi: 10.1016/0014-5793(89)81196-2. [DOI] [PubMed] [Google Scholar]
  • 72.Sikorski AF, Michalak K, Bobrowska M. Interaction of spectrin with phospholipids. Quenching of spectrin intrinsic fluorescence by phospholipid suspensions. Biochim. Biophys. Acta. 1987;904:55–60. doi: 10.1016/0005-2736(87)90086-1. [DOI] [PubMed] [Google Scholar]
  • 73.Sikorski AF, Michalak K, Bobrowska M, Kozubek A. Interaction of spectrin with some amphipatic compunds. Stud. Biophys. 1987;121:183–191. [Google Scholar]
  • 74.Sikorski AF. Interaction of spectrin with hydrophobic agaroses. Acta Biochim. Pol. 1988;35:19–27. [PubMed] [Google Scholar]
  • 75.Grzybek M, Chorzalska A, Bok E, Hryniewicz-Jankowska A, Czogalla A, Diakowski W, Sikorski AF. Spectrin-phospholipid interactions. Existence of multiple kinds of binding sites? Chem. Phys. Lipids. 2006;141:133–141. doi: 10.1016/j.chemphyslip.2006.02.008. [DOI] [PubMed] [Google Scholar]
  • 76.Sikorski AF, Czogalla A, Hryniewicz-Jankowska A, Bok E, Plażuk E, Diakowski W, Chorzalska A, Kolondra A, Langner M, Grzybek M. Interactions of erythroid and non-erythroid spectrins and other membrane skeletal proteins with lipid mono- and bilayers. In: Leitmannova LA, editor. Advances in Planar Lipid Bilayers and Liposomes. 2008. pp. 81–102. [Google Scholar]
  • 77.Bialkowska K, Zembron A, Sikorski AF. Ankyrin inhibits binding of erythrocyte spectrin to phospholipid vesicles. Biochim. Biophys. Acta. 1994;1191:21–26. doi: 10.1016/0005-2736(94)90228-3. [DOI] [PubMed] [Google Scholar]
  • 78.O’Toole PJ, Morrison IE, Cherry RJ. Investigations of spectrin-lipid interactions using fluoresceinphosphatidylethanolamine as a membrane probe. Biochim. Biophys. Acta. 2000;1466:39–46. doi: 10.1016/s0005-2736(00)00168-1. [DOI] [PubMed] [Google Scholar]
  • 79.Michalak K, Bobrowska M, Sikorski AF. Interaction of bovine erythrocyte spectrin with aminophospholipid liposomes. Gen. Physiol. Biophys. 1993;12:163–170. [PubMed] [Google Scholar]
  • 80.Diakowski W, Sikorski AF. Interaction of brain spectrin (fodrin) with phospholipids. Biochemistry. 1995;34:13252–13258. doi: 10.1021/bi00040a041. [DOI] [PubMed] [Google Scholar]
  • 81.Juliano RL, Kimelberg HK, Papahadjopoulos D. Synergistic effects of a membrane protein (spectrin) and Ca 2+ on the Na + permeability of phospholipid vesicles. Biochim. Biophys. Acta. 1971;241:894–905. doi: 10.1016/0005-2736(71)90017-4. [DOI] [PubMed] [Google Scholar]
  • 82.Bandorowicz-Pikula J, Sikorski AF, Bialkowska K, Sobota A. Interaction of annexins IV and VI with phosphatidylserine in the presence of Ca2+: monolayer and proteolytic study. Mol. Membr. Biol. 1996;13:241–250. doi: 10.3109/09687689609160602. [DOI] [PubMed] [Google Scholar]
  • 83.Sobota A, Bandorowicz J, Jezierski A, Sikorski AF. The effect of annexin IV and VI on the fluidity of phosphatidylserine/phosphatidylcholine bilayers studied with the use of 5-deoxylstearate spin label. FEBS Lett. 1993;315:178–182. doi: 10.1016/0014-5793(93)81158-v. [DOI] [PubMed] [Google Scholar]
  • 84.Czogalla A, Sikorski AF. Spectrin and calpain: a ‘target’ and a ‘sniper’ in the pathology of neuronal cells. Cell. Mol. Life Sci. 2005;62:1913–1924. doi: 10.1007/s00018-005-5097-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 85.Lofvenberg L, Backman L. Calpain-induced proteolysis of betaspectrins. FEBS Lett. 1999;443:89–92. doi: 10.1016/s0014-5793(98)01697-4. [DOI] [PubMed] [Google Scholar]
  • 86.Ray S, Chakrabarti A. Membrane interaction of erythroid spectrin: surface-density-dependent high-affinity binding to phosphatidylethanolamine. Mol. Membr. Biol. 2004;21:93–100. doi: 10.1080/09687680310001625800. [DOI] [PubMed] [Google Scholar]
  • 87.Verkleij AJ, Zwaal RF, Roelofsen B, Comfurius P, Kastelijn D, van Deenen LL. The asymmetric distribution of phospholipids in the human red cell membrane. A combined study using phospholipases and freeze-etch electron microscopy. Biochim. Biophys. Acta. 1973;323:178–193. doi: 10.1016/0005-2736(73)90143-0. [DOI] [PubMed] [Google Scholar]
  • 88.van Zwieten R, Bochem AE, Hilarius PM, van Bruggen R, Bergkamp F, Hovingh GK, Verhoeven AJ. The cholesterol content of the erythrocyte membrane is an important determinant of phosphatidylserine exposure. Biochim. Biophys. Acta. 2012;1821:1493–1500. doi: 10.1016/j.bbalip.2012.08.008. [DOI] [PubMed] [Google Scholar]
  • 89.Diakowski W, Prychidny A, Swistak M, Nietubyc M, Bialkowska K, Szopa J, Sikorski AF. Brain spectrin (fodrin) interacts with phospholipids as revealed by intrinsic fluorescence quenching and monolayer experiments. Biochem. J. 1999;338:83–90. [PMC free article] [PubMed] [Google Scholar]
  • 90.Diakowski W, Sikorski AF. Brain spectrin exerts much stronger effect on anionic phospholipid monolayers than erythroid spectrin. Biochim. Biophys. Acta. 2002;1564:403–411. doi: 10.1016/s0005-2736(02)00476-5. [DOI] [PubMed] [Google Scholar]
  • 91.Diakowski W, Szopa J, Sikorski AF. Occurrence of lipid receptors inferred from brain and erythrocyte spectrins binding NaOH-extracted and protease-treated neuronal and erythrocyte membranes. Biochim. Biophys. Acta. 2003;1611:115–122. doi: 10.1016/s0005-2736(03)00032-4. [DOI] [PubMed] [Google Scholar]
  • 92.Diakowski W, Ozimek L, Bielska E, Bem S, Langner M, Sikorski AF. Cholesterol affects spectrin-phospholipid interactions in a manner different from changes resulting from alterations in membrane fluidity due to fatty acyl chain composition. Biochim. Biophys. Acta. 2006;1758:4–12. doi: 10.1016/j.bbamem.2005.11.009. [DOI] [PubMed] [Google Scholar]
  • 93.Simons K, Sampaio JL. Membrane organization and lipid rafts. Cold Spring Harb. Perspect. Biol. 2011;3:a004697. doi: 10.1101/cshperspect.a004697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 94.Grzybek M, Kozubek A, Dubielecka P, Sikorski AF. Rafts—the current picture. Folia Histochem. Cytobiol. 2005;43:3–10. [PubMed] [Google Scholar]
  • 95.Thompson JM, Ellis RE, Green EM, Winlove CP, Petrov PG. Spectrin maintains the lateral order in phosphatidylserine monolayers. Chem. Phys. Lipids. 2008;151:66–68. doi: 10.1016/j.chemphyslip.2007.09.003. [DOI] [PubMed] [Google Scholar]
  • 96.Manno S, Takakuwa Y, Mohandas N. Identification of a functional role for lipid asymmetry in biological membranes: Phosphatidylserineskeletal protein interactions modulate membrane stability. Proc. Natl. Acad. Sci. U S A. 2002;99:1943–1948. doi: 10.1073/pnas.042688399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 97.Manno S, Mohandas N, Takakuwa Y. ATP-dependent mechanism protects spectrin against glycation in human erythrocytes. J. Biol. Chem. 2010;285:33923–33929. doi: 10.1074/jbc.M110.126896. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 98.Sarkis J, Hubert JF, Legrand B, Robert E, Cheron A, Jardin J, Hitti E, Le Rumeur E, Vie V. Spectrin-like repeats 11–15 of human dystrophin show adaptations to a lipidic environment. J. Biol. Chem. 2011;286:30481–30491. doi: 10.1074/jbc.M111.243881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 99.Le Rumeur E, Fichou Y, Pottier S, Gaboriau F, Rondeau-Mouro C, Vincent M, Gallay J, Bondon A. Interaction of dystrophin rod domain with membrane phospholipids. Evidence of a close proximity between tryptophan residues and lipids. J. Biol. Chem. 2003;278:5993–6001. doi: 10.1074/jbc.M207321200. [DOI] [PubMed] [Google Scholar]
  • 100.DeWolf C, McCauley P, Sikorski AF, Winlove CP, Bailey AI, Kahana E, Pinder JC, Gratzer WB. Interaction of dystrophin fragments with model membranes. Biophys. J. 1997;72:2599–2604. doi: 10.1016/S0006-3495(97)78903-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 101.An X, Guo X, Wu Y, Mohandas N. Phosphatidylserine binding sites in red cell spectrin. Blood Cells Mol. Dis. 2004;32:430–432. doi: 10.1016/j.bcmd.2004.02.001. [DOI] [PubMed] [Google Scholar]
  • 102.An X, Guo X, Sum H, Morrow J, Gratzer W, Mohandas N. Phosphatidylserine binding sites in erythroid spectrin: location and implications for membrane stability. Biochemistry. 2004;43:310–315. doi: 10.1021/bi035653h. [DOI] [PubMed] [Google Scholar]
  • 103.Hryniewicz-Jankowska A, Bok E, Dubielecka P, Chorzalska A, Diakowski W, Jezierski A, Lisowski M, Sikorski AF. Mapping of an ankyrinsensitive, phosphatidylethanolamine/phosphatidylcholine mono- and bi-layer binding site in erythroid beta-spectrin. Biochem. J. 2004;382:677–685. doi: 10.1042/BJ20040358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 104.Wolny M, Grzybek M, Bok E, Chorzalska A, Lenoir M, Czogalla A, Adamczyk K, Kolondra A, Diakowski W, Overduin M, Sikorski AF. Key amino acid residues of ankyrin-sensitive phosphatidylethanolamine/phosphatidylcholine-lipid binding site of betaI-spectrin. PLoS One. 2011;6:e21538. doi: 10.1371/journal.pone.0021538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 105.Bok E, Plazuk E, Hryniewicz-Jankowska A, Chorzalska A, Szmaj A, Dubielecka PM, Stebelska K, Diakowski W, Lisowski M, Langner M, Sikorski AF. Lipid-binding role of betaII-spectrin ankyrin-binding domain. Cell. Biol. Int. 2007;31:1482–1494. doi: 10.1016/j.cellbi.2007.06.014. [DOI] [PubMed] [Google Scholar]
  • 106.Baines AJ. The spectrin-ankyrin-4.1-adducin membrane skeleton: adapting eukaryotic cells to the demands of animal life. Protoplasma. 2010;244:99–131. doi: 10.1007/s00709-010-0181-1. [DOI] [PubMed] [Google Scholar]
  • 107.Le Rumeur E, Hubert JF, Winder SJ. A new twist to coiled coil. FEBS Lett. 2012;586:2717–2722. doi: 10.1016/j.febslet.2012.05.004. [DOI] [PubMed] [Google Scholar]
  • 108.Kahana E, Gratzer WB. Minimum folding unit of dystrophin rod domain. Biochemistry. 1995;34:8110–8114. doi: 10.1021/bi00025a017. [DOI] [PubMed] [Google Scholar]
  • 109.Legardinier S, Raguenes-Nicol C, Tascon C, Rocher C, Hardy S, Hubert JF, Le Rumeur E. Mapping of the lipid-binding and stability properties of the central rod domain of human dystrophin. J. Mol. Biol. 2009;389:546–558. doi: 10.1016/j.jmb.2009.04.025. [DOI] [PubMed] [Google Scholar]
  • 110.Sarkis J, Vie V, Winder SJ, Renault A, Le Rumeur E, Hubert JF. Resisting sarcolemmal rupture: dystrophin repeats increase membraneactin stiffness. FASEB J. 2013;27:359–367. doi: 10.1096/fj.12-208967. [DOI] [PubMed] [Google Scholar]
  • 111.Vie V, Legardinier S, Chieze L, Le Bihan O, Qin Y, Sarkis J, Hubert JF, Renault A, Desbat B, Le Rumeur E. Specific anchoring modes of two distinct dystrophin rod sub-domains interacting in phospholipid Langmuir films studied by atomic force microscopy and PMIRRAS. Biochim. Biophys. Acta. 2010;1798:1503–1511. doi: 10.1016/j.bbamem.2010.04.005. [DOI] [PubMed] [Google Scholar]
  • 112.Czogalla A, Grzymajlo K, Jezierski A, Sikorski AF. Phospholipidinduced structural changes to an erythroid beta spectrin ankyrin-dependent lipid-binding site. Biochim. Biophys. Acta. 2008;1778:2612–2620. doi: 10.1016/j.bbamem.2008.07.020. [DOI] [PubMed] [Google Scholar]
  • 113.An X, Guo X, Gratzer W, Mohandas N. Phospholipid binding by proteins of the spectrin family: a comparative study. Biochem. Biophys. Res. Commun. 2005;327:794–800. doi: 10.1016/j.bbrc.2004.12.063. [DOI] [PubMed] [Google Scholar]
  • 114.An X, Debnath G, Guo X, Liu S, Lux SE, Baines A, Gratzer W, Mohandas N. Identification and functional characterization of protein 4.1R and actin-binding sites in erythrocyte beta spectrin: regulation of the interactions by phosphatidylinositol-4, 5-bisphosphate. Biochemistry. 2005;44:10681–10688. doi: 10.1021/bi047331z. [DOI] [PubMed] [Google Scholar]
  • 115.Franzot G, Sjoblom B, Gautel M, Djinovic Carugo K. The crystal structure of the actin-binding domain from alpha-actinin in its closed conformation: structural insight into phospholipid regulation of alphaactinin. J. Mol. Biol. 2005;348:151–165. doi: 10.1016/j.jmb.2005.01.002. [DOI] [PubMed] [Google Scholar]
  • 116.Young P, Gautel M. The interaction of titin and alpha-actinin is controlled by a phospholipid-regulated intramolecular pseudoligand mechanism. EMBO J. 2000;19:6331–6340. doi: 10.1093/emboj/19.23.6331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 117.Hyvonen M, Macias MJ, Nilges M, Oschkinat H, Saraste M, Wilmanns M. Structure of the binding site for inositol phosphates in a PH domain. EMBO J. 1995;14:4676–4685. doi: 10.1002/j.1460-2075.1995.tb00149.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 118.Scheffzek K, Welti S. Pleckstrin homology (PH) like domains — versatile modules in protein-protein interaction platforms. FEBS Lett. 2012;586:2662–2673. doi: 10.1016/j.febslet.2012.06.006. [DOI] [PubMed] [Google Scholar]
  • 119.Lemmon MA. Pleckstrin homology domains: two halves make a hole? Cell. 2005;120:574–576. doi: 10.1016/j.cell.2005.02.023. [DOI] [PubMed] [Google Scholar]
  • 120.Lemmon MA, Ferguson KM, Abrams CS. Pleckstrin homology domains and the cytoskeleton. FEBS Lett. 2002;513:71–76. doi: 10.1016/s0014-5793(01)03243-4. [DOI] [PubMed] [Google Scholar]
  • 121.Godi A, Santone I, Pertile P, Devarajan P, Stabach PR, Morrow JS, Di Tullio G, Polishchuk R, Petrucci TC, Luini A, De Matteis MA. ADP ribosylation factor regulates spectrin binding to the Golgi complex. Proc. Natl. Acad. Sci. USA. 1998;95:8607–8612. doi: 10.1073/pnas.95.15.8607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 122.Muresan V, Stankewich MC, Steffen W, Morrow JS, Holzbaur EL, Schnapp BJ. Dynactin-dependent, dynein-driven vesicle transport in the absence of membrane proteins: a role for spectrin and acidic phospholipids. Mol. Cell. 2001;7:173–183. doi: 10.1016/s1097-2765(01)00165-4. [DOI] [PubMed] [Google Scholar]
  • 123.Das A, Base C, Manna D, Cho W, Dubreuil RR. Unexpected complexity in the mechanisms that target assembly of the spectrin cytoskeleton. J. Biol. Chem. 2008;283:12643–12653. doi: 10.1074/jbc.M800094200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 124.Bialkowska K, Zembron A, Sikorski AF. Ankyrin shares a binding site with phospholipid vesicles on erythrocyte spectrin. Acta Biochim. Pol. 1994;41:155–157. [PubMed] [Google Scholar]
  • 125.Bialkowska K, Lesniewski J, Nietubyc M, Sikorski AF. Interaction of spectrin with phospholipids is inhibited by isolated erythrocyte ankyrin. A monolayer study. Cell. Mol. Biol. Lett. 1999;4:203–218. [Google Scholar]
  • 126.Kennedy SP, Warren SL, Forget BG, Morrow JS. Ankyrin binds to the 15th repetitive unit of erythroid and non-erythroid beta-spectrin. J. Cell Biol. 1991;115:267–277. doi: 10.1083/jcb.115.1.267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 127.Stabach PR, Simonovic I, Ranieri MA, Aboodi MS, Steitz TA, Simonovic M, Morrow JS. The structure of the ankyrin-binding site of beta-spectrin reveals how tandem spectrin-repeats generate unique ligand-binding properties. Blood. 2009;113:5377–5384. doi: 10.1182/blood-2008-10-184291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 128.Czogalla A, Jaszewski AR, Diakowski W, Bok E, Jezierski A, Sikorski AF. Structural insight into an ankyrin-sensitive lipid-binding site of erythroid beta-spectrin. Mol. Membr. Biol. 2007;24:215–224. doi: 10.1080/09687860601102427. [DOI] [PubMed] [Google Scholar]
  • 129.Davis L, Abdi K, Machius M, Brautigam C, Tomchick DR, Bennett V, Michaely P. Localization and structure of the ankyrin-binding site on beta2-spectrin. J. Biol. Chem. 2009;284:6982–6987. doi: 10.1074/jbc.M809245200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 130.Ipsaro JJ, Huang L, Mondragon A. Structures of the spectrin-ankyrin interaction binding domains. Blood. 2009;113:5385–5393. doi: 10.1182/blood-2008-10-184358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 131.Ipsaro JJ, Mondragon A. Structural basis for spectrin recognition by ankyrin. Blood. 2010;115:4093–4101. doi: 10.1182/blood-2009-11-255604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 132.Pazdzior G, Chorzalska A, Czogalla A, Borowik T, Sikorski AF, Langner M. Fluorescence approach to evaluating conformational changes upon binding of beta-spectrin ankyrin-binding domain mutants with the lipid bilayer. Gen. Physiol. Biophys. 2009;28:283–293. doi: 10.4149/gpb_2009_03_283. [DOI] [PubMed] [Google Scholar]
  • 133.Grum VL, Li D, MacDonald RI, Mondragon A. Structures of two repeats of spectrin suggest models of flexibility. Cell. 1999;98:523–535. doi: 10.1016/s0092-8674(00)81980-7. [DOI] [PubMed] [Google Scholar]
  • 134.Chorzalska A, Lach A, Borowik T, Wolny M, Hryniewicz-Jankowska A, Kolondra A, Langner M, Sikorski AF. The effect of the lipidbinding site of the ankyrin-binding domain of erythroid beta-spectrin on the properties of natural membranes and skeletal structures. Cell. Mol. Biol. Lett. 2010;15:406–423. doi: 10.2478/s11658-010-0012-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 135.Drin G, Antonny B. Amphipathic helices and membrane curvature. FEBS Lett. 2010;584:1840–1847. doi: 10.1016/j.febslet.2009.10.022. [DOI] [PubMed] [Google Scholar]
  • 136.Sikorski AF, Jezierski A. Influence of spectrin on the fluidity of erythrocyte membrane. Stud. Biophys. 1986;113:193–201. [Google Scholar]

Articles from Cellular & Molecular Biology Letters are provided here courtesy of BMC

RESOURCES