Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1994 Apr;93(4):1430–1438. doi: 10.1172/JCI117120

The fodrin-ankyrin cytoskeleton of choroid plexus preferentially colocalizes with apical Na+K(+)-ATPase rather than with basolateral anion exchanger AE2.

S L Alper 1, A Stuart-Tilley 1, C F Simmons 1, D Brown 1, D Drenckhahn 1
PMCID: PMC294156  PMID: 8163647

Abstract

A unique feature of the choroid plexus as a single-layer epithelium is its localization of Na+K(+)-ATPase at its apical (lumenal) surface. In contrast, a band 3 (AE1)-related anion exchanger protein has been localized to the basolateral surface of the choroid plexus. Both Na+K(+)-ATPase and AE1 in other tissues have been shown to bind via ankyrin to the spectrin-actin-based membrane cytoskeleton. Since linkage of integral membrane proteins to the membrane cytoskeleton is important for their restriction to specialized domains of the cell surface, we investigated the polarity of the choroid plexus membrane cytoskeleton. We developed isoform-specific antibodies to confirm the identity of choroid plexus band 3-related polypeptide as AE2. We demonstrated that ankyrin, fodrin/spectrin, actin, myosin, and alpha-actinin are predominantly apical in choroid plexus and preferentially colocalize with apical Na+K(+)-ATPase rather than with basolateral anion exchanger AE2. Colchicine administration did not alter the polarity of apical cytoskeletal and transport proteins or basolateral AE2 in choroid plexus, suggesting that biosynthetic targeting of these proteins is not microtubule dependent. In choroid plexus papilloma, Na+K(+)-ATPase and AE2 were decreased in amount and failed to preserve their polarized distributions.

Full text

PDF
1430

Images in this article

1431Image
on p.1431
1432Image
on p.1432
1432Image
on p.1432
1433Image
on p.1433
1433Image
on p.1433
1433Image
on p.1433
1434Image
on p.1434
1435Image
on p.1435
1436Image
on p.1436
1436Image
on p.1436
1437Image
on p.1437

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Achler C., Filmer D., Merte C., Drenckhahn D. Role of microtubules in polarized delivery of apical membrane proteins to the brush border of the intestinal epithelium. J Cell Biol. 1989 Jul;109(1):179–189. doi: 10.1083/jcb.109.1.179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aldred A. R., Dickson P. W., Marley P. D., Schreiber G. Distribution of transferrin synthesis in brain and other tissues in the rat. J Biol Chem. 1987 Apr 15;262(11):5293–5297. [PubMed] [Google Scholar]
  3. Aldred A. R., Grimes A., Schreiber G., Mercer J. F. Rat ceruloplasmin. Molecular cloning and gene expression in liver, choroid plexus, yolk sac, placenta, and testis. J Biol Chem. 1987 Feb 25;262(6):2875–2878. [PubMed] [Google Scholar]
  4. Alper S. L., Kopito R. R., Libresco S. M., Lodish H. F. Cloning and characterization of a murine band 3-related cDNA from kidney and from a lymphoid cell line. J Biol Chem. 1988 Nov 15;263(32):17092–17099. [PubMed] [Google Scholar]
  5. Alper S. L., Natale J., Gluck S., Lodish H. F., Brown D. Subtypes of intercalated cells in rat kidney collecting duct defined by antibodies against erythroid band 3 and renal vacuolar H+-ATPase. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5429–5433. doi: 10.1073/pnas.86.14.5429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Alper S. L. The band 3-related anion exchanger (AE) gene family. Annu Rev Physiol. 1991;53:549–564. doi: 10.1146/annurev.ph.53.030191.003001. [DOI] [PubMed] [Google Scholar]
  7. Apodaca G., Bomsel M., Arden J., Breitfeld P. P., Tang K., Mostov K. E. The polymeric immunoglobulin receptor. A model protein to study transcytosis. J Clin Invest. 1991 Jun;87(6):1877–1882. doi: 10.1172/JCI115211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Aunis D., Bader M. F. The cytoskeleton as a barrier to exocytosis in secretory cells. J Exp Biol. 1988 Sep;139:253–266. doi: 10.1242/jeb.139.1.253. [DOI] [PubMed] [Google Scholar]
  9. Bacallao R., Antony C., Dotti C., Karsenti E., Stelzer E. H., Simons K. The subcellular organization of Madin-Darby canine kidney cells during the formation of a polarized epithelium. J Cell Biol. 1989 Dec;109(6 Pt 1):2817–2832. doi: 10.1083/jcb.109.6.2817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Bartles J. R., Feracci H. M., Stieger B., Hubbard A. L. Biogenesis of the rat hepatocyte plasma membrane in vivo: comparison of the pathways taken by apical and basolateral proteins using subcellular fractionation. J Cell Biol. 1987 Sep;105(3):1241–1251. doi: 10.1083/jcb.105.3.1241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Bomsel M., Mostov K. Role of heterotrimeric G proteins in membrane traffic. Mol Biol Cell. 1992 Dec;3(12):1317–1328. doi: 10.1091/mbc.3.12.1317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Brown D., Sabolic I., Gluck S. Colchicine-induced redistribution of proton pumps in kidney epithelial cells. Kidney Int Suppl. 1991 Jul;33:S79–S83. [PubMed] [Google Scholar]
  13. Cole T., Dickson P. W., Esnard F., Averill S., Risbridger G. P., Gauthier F., Schreiber G. The cDNA structure and expression analysis of the genes for the cysteine proteinase inhibitor cystatin C and for beta 2-microglobulin in rat brain. Eur J Biochem. 1989 Dec 8;186(1-2):35–42. doi: 10.1111/j.1432-1033.1989.tb15174.x. [DOI] [PubMed] [Google Scholar]
  14. Davis J. Q., McLaughlin T., Bennett V. Ankyrin-binding proteins related to nervous system cell adhesion molecules: candidates to provide transmembrane and intercellular connections in adult brain. J Cell Biol. 1993 Apr;121(1):121–133. doi: 10.1083/jcb.121.1.121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Drenckhahn D., Bennett V. Polarized distribution of Mr 210,000 and 190,000 analogs of erythrocyte ankyrin along the plasma membrane of transporting epithelia, neurons and photoreceptors. Eur J Cell Biol. 1987 Jun;43(3):479–486. [PubMed] [Google Scholar]
  16. Drenckhahn D., Dermietzel R. Organization of the actin filament cytoskeleton in the intestinal brush border: a quantitative and qualitative immunoelectron microscope study. J Cell Biol. 1988 Sep;107(3):1037–1048. doi: 10.1083/jcb.107.3.1037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Drenckhahn D., Mannherz H. G. Distribution of actin and the actin-associated proteins myosin, tropomyosin, alpha-actinin, vinculin, and villin in rat and bovine exocrine glands. Eur J Cell Biol. 1983 May;30(2):167–176. [PubMed] [Google Scholar]
  18. Drenckhahn D., Schlüter K., Allen D. P., Bennett V. Colocalization of band 3 with ankyrin and spectrin at the basal membrane of intercalated cells in the rat kidney. Science. 1985 Dec 13;230(4731):1287–1289. doi: 10.1126/science.2933809. [DOI] [PubMed] [Google Scholar]
  19. Duan W., Cole T., Schreiber G. Cloning and nucleotide sequencing of transthyretin (prealbumin) cDNA from rat choroid plexus and liver. Nucleic Acids Res. 1989 May 25;17(10):3979–3979. doi: 10.1093/nar/17.10.3979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Eilers U., Klumperman J., Hauri H. P. Nocodazole, a microtubule-active drug, interferes with apical protein delivery in cultured intestinal epithelial cells (Caco-2). J Cell Biol. 1989 Jan;108(1):13–22. doi: 10.1083/jcb.108.1.13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ercolani L., Brown D., Stuart-Tilley A., Alper S. L. Colocalization of GAPDH and band 3 (AE1) proteins in rat erythrocytes and kidney intercalated cell membranes. Am J Physiol. 1992 May;262(5 Pt 2):F892–F896. doi: 10.1152/ajprenal.1992.262.5.F892. [DOI] [PubMed] [Google Scholar]
  22. Ernst S. A., Palacios J. R., 2nd, Siegel G. J. Immunocytochemical localization of Na+,K+-ATPase catalytic polypeptide in mouse choroid plexus. J Histochem Cytochem. 1986 Feb;34(2):189–195. doi: 10.1177/34.2.3003182. [DOI] [PubMed] [Google Scholar]
  23. Fishkind D. J., Bonder E. M., Begg D. A. Subcellular localization of sea urchin egg spectrin: evidence for assembly of the membrane-skeleton on unique classes of vesicles in eggs and embryos. Dev Biol. 1990 Dec;142(2):439–452. doi: 10.1016/0012-1606(90)90366-q. [DOI] [PubMed] [Google Scholar]
  24. Gundersen D., Orlowski J., Rodriguez-Boulan E. Apical polarity of Na,K-ATPase in retinal pigment epithelium is linked to a reversal of the ankyrin-fodrin submembrane cytoskeleton. J Cell Biol. 1991 Mar;112(5):863–872. doi: 10.1083/jcb.112.5.863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Gundersen D., Powell S. K., Rodriguez-Boulan E. Apical polarization of N-CAM in retinal pigment epithelium is dependent on contact with the neural retina. J Cell Biol. 1993 Apr;121(2):335–343. doi: 10.1083/jcb.121.2.335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Gutmann E. J., Niles J. L., McCluskey R. T., Brown D. Colchicine-induced redistribution of an apical membrane glycoprotein (gp330) in proximal tubules. Am J Physiol. 1989 Aug;257(2 Pt 1):C397–C407. doi: 10.1152/ajpcell.1989.257.2.C397. [DOI] [PubMed] [Google Scholar]
  27. Haller C., Alper S. L. Nonpolarized surface distribution and delivery of human CD7 in polarized MDCK cells. Am J Physiol. 1993 Oct;265(4 Pt 1):C1069–C1079. doi: 10.1152/ajpcell.1993.265.4.C1069. [DOI] [PubMed] [Google Scholar]
  28. Hunziker W., Mellman I. Expression of macrophage-lymphocyte Fc receptors in Madin-Darby canine kidney cells: polarity and transcytosis differ for isoforms with or without coated pit localization domains. J Cell Biol. 1989 Dec;109(6 Pt 2):3291–3302. doi: 10.1083/jcb.109.6.3291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Koob R., Kraemer D., Trippe G., Aebi U., Drenckhahn D. Association of kidney and parotid Na+, K(+)-ATPase microsomes with actin and analogs of spectrin and ankyrin. Eur J Cell Biol. 1990 Oct;53(1):93–100. [PubMed] [Google Scholar]
  30. Koob R., Zimmermann M., Schoner W., Drenckhahn D. Colocalization and coprecipitation of ankyrin and Na+,K+-ATPase in kidney epithelial cells. Eur J Cell Biol. 1988 Feb;45(2):230–237. [PubMed] [Google Scholar]
  31. Lambert S., Bennett V. From anemia to cerebellar dysfunction. A review of the ankyrin gene family. Eur J Biochem. 1993 Jan 15;211(1-2):1–6. doi: 10.1111/j.1432-1033.1993.tb19863.x. [DOI] [PubMed] [Google Scholar]
  32. Lindsey A. E., Schneider K., Simmons D. M., Baron R., Lee B. S., Kopito R. R. Functional expression and subcellular localization of an anion exchanger cloned from choroid plexus. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5278–5282. doi: 10.1073/pnas.87.14.5278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. McNeill H., Ozawa M., Kemler R., Nelson W. J. Novel function of the cell adhesion molecule uvomorulin as an inducer of cell surface polarity. Cell. 1990 Jul 27;62(2):309–316. doi: 10.1016/0092-8674(90)90368-o. [DOI] [PubMed] [Google Scholar]
  34. Mercer R. W., Schneider J. W., Savitz A., Emanuel J., Benz E. J., Jr, Levenson R. Rat-brain Na,K-ATPase beta-chain gene: primary structure, tissue-specific expression, and amplification in ouabain-resistant HeLa C+ cells. Mol Cell Biol. 1986 Nov;6(11):3884–3890. doi: 10.1128/mcb.6.11.3884. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Nathanson J. A., Chun L. L. Immunological function of the blood-cerebrospinal fluid barrier. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1684–1688. doi: 10.1073/pnas.86.5.1684. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Nelson W. J., Shore E. M., Wang A. Z., Hammerton R. W. Identification of a membrane-cytoskeletal complex containing the cell adhesion molecule uvomorulin (E-cadherin), ankyrin, and fodrin in Madin-Darby canine kidney epithelial cells. J Cell Biol. 1990 Feb;110(2):349–357. doi: 10.1083/jcb.110.2.349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Palmiter R. D., Chen H. Y., Messing A., Brinster R. L. SV40 enhancer and large-T antigen are instrumental in development of choroid plexus tumours in transgenic mice. Nature. 1985 Aug 1;316(6027):457–460. doi: 10.1038/316457a0. [DOI] [PubMed] [Google Scholar]
  38. Patel V. P., Lodish H. F. A fibronectin matrix is required for differentiation of murine erythroleukemia cells into reticulocytes. J Cell Biol. 1987 Dec;105(6 Pt 2):3105–3118. doi: 10.1083/jcb.105.6.3105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Rodriguez-Boulan E., Powell S. K. Polarity of epithelial and neuronal cells. Annu Rev Cell Biol. 1992;8:395–427. doi: 10.1146/annurev.cb.08.110192.002143. [DOI] [PubMed] [Google Scholar]
  40. Rothman J. E., Orci L. Molecular dissection of the secretory pathway. Nature. 1992 Jan 30;355(6359):409–415. doi: 10.1038/355409a0. [DOI] [PubMed] [Google Scholar]
  41. Saito Y., Wright E. M. Bicarbonate transport across the frog choroid plexus and its control by cyclic nucleotides. J Physiol. 1983 Mar;336:635–648. doi: 10.1113/jphysiol.1983.sp014602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Shull G. E., Greeb J., Lingrel J. B. Molecular cloning of three distinct forms of the Na+,K+-ATPase alpha-subunit from rat brain. Biochemistry. 1986 Dec 16;25(25):8125–8132. doi: 10.1021/bi00373a001. [DOI] [PubMed] [Google Scholar]
  43. Siemers Krzeminski K. A., Wilson Hammerton R., Mays R. W., Ryan T. A., Wollner D. A., Nelson W. J. Response. Science. 1993 Apr 23;260(5107):554–556. doi: 10.1126/science.260.5107.554. [DOI] [PubMed] [Google Scholar]
  44. Smith P. R., Bradford A. L., Joe E. H., Angelides K. J., Benos D. J., Saccomani G. Gastric parietal cell H(+)-K(+)-ATPase microsomes are associated with isoforms of ankyrin and spectrin. Am J Physiol. 1993 Jan;264(1 Pt 1):C63–C70. doi: 10.1152/ajpcell.1993.264.1.C63. [DOI] [PubMed] [Google Scholar]
  45. Sweadner K. J. Isozymes of the Na+/K+-ATPase. Biochim Biophys Acta. 1989 May 9;988(2):185–220. doi: 10.1016/0304-4157(89)90019-1. [DOI] [PubMed] [Google Scholar]
  46. Watts A. G., Sanchez-Watts G., Emanuel J. R., Levenson R. Cell-specific expression of mRNAs encoding Na+,K(+)-ATPase alpha- and beta-subunit isoforms within the rat central nervous system. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7425–7429. doi: 10.1073/pnas.88.16.7425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Zlokovic B. V., Mackic J. B., Wang L., McComb J. G., McDonough A. Differential expression of Na,K-ATPase alpha and beta subunit isoforms at the blood-brain barrier and the choroid plexus. J Biol Chem. 1993 Apr 15;268(11):8019–8025. [PubMed] [Google Scholar]
  48. Zurzolo C., Rodriguez-Boulan E. Delivery of Na+,K(+)-ATPase in polarized epithelial cells. Science. 1993 Apr 23;260(5107):550–556. doi: 10.1126/science.8386394. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES