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. 2004 Feb 24;1(4):617–623. doi: 10.1016/0955-0674(89)90024-0

Sorting signals

PP Breitfeld ∗∗, JE Casanova ∗, NE Simistert †, SA Ross ∗, WC McKinnon ∗∗, KE Mostov ∗
PMCID: PMC7135832  PMID: 2576381

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References

  • 1.Kornfeld S. Trafficking of lysomal enzymes. FASEB J. 1987;1:462–468. doi: 10.1096/fasebj.1.6.3315809. Of interest. [DOI] [PubMed] [Google Scholar]; Very readable review of the M-6-P signal and its receptor, which target enzymes to lysosomes. The authors' laboratory has been the source of much of our knowledge in this field.
  • 2.Bartles J.R., Hubbard A.L. Plasma membrane protein sorting in epithelial cells: do secretory pathways hold the key? Trends Biochem Sci. 1988;13:181–184. doi: 10.1016/0968-0004(88)90147-8. Of interest. [DOI] [PubMed] [Google Scholar]; Compares data on secretion and membrane traffic in the cannonical MDCK system with the authors' observations on hepatocytes. Raises several useful questions about the relationship between traffic of membrane and soluble proteins.
  • 3.Kelly R.B. The cell biology of the nerve terminal - review. Neuron. 1988;1:431–437. doi: 10.1016/0896-6273(88)90174-2. Of interest. [DOI] [PMC free article] [PubMed] [Google Scholar]; Although this review is officially about neuronal cells, it is from a strong cell biological perspective. It synthesizes a wealth of information on targeting, exocytosis and endocytosis, especially in cells with a regulated pathway.
  • 4.Simons K., Van Meer G. Lipid sorting in epithelial cells. Biochemistry. 1988;27:6197–6202. doi: 10.1021/bi00417a001. Of outstanding interest. [DOI] [PubMed] [Google Scholar]; Summarizes work, primarily from the authors' laboratories, on the specific sorting of glycolipids to the apical surface of epithelial cells. They make the provocative hypothesis that these lipids self-aggregate into sorted domains and that these mediate the apical targeting of proteins. They also argue that the default pathway for membrane proteins is generally to the basolateral surface.
  • 5.Brodsky F.M. Living with clathrin: its role in intracellular membrane traffic. Science. 1988;242:1396–1402. doi: 10.1126/science.2904698. Of interest. [DOI] [PubMed] [Google Scholar]; The role of clathrin has been controversial, because certain yeast mutants can survive without it. The author presents a balanced view of the structure and function of clathrin.
  • 6.Pelham H.R.B. Evidence that luminal ER proteins are sorted from secreted proteins in a post-ER compartment. EMBO J. 1988;7:913–918. doi: 10.1002/j.1460-2075.1988.tb02896.x. Of interest. [DOI] [PMC free article] [PubMed] [Google Scholar]; A lysosomal enzyme, cathepsin D, had the sequence KDEL added to its carboxy terminus, and was retained in the ER However, its oligosaccharides received the M-6-P marker, indicating that it reaches the cis Golgi and is retrieved to the ER.
  • 7.Pelham H.R.B., Hardwick K.G., Lewis M.J. Sorting of soluble ER proteins in yeast. EMBO J. 1988;7:1757–1762. doi: 10.1002/j.1460-2075.1988.tb03005.x. Of outstanding interest. [DOI] [PMC free article] [PubMed] [Google Scholar]; In yeast cells, HDEL (and not KDEL) is shown to be the signal for ER retention. 3 groups of mutants that are defective in this retention function are identified. 1 of these may be the HDEL receptor itself.
  • 8.Poruchynsky M.S., Atkinson P.H. Primary sequence domains required for the retention of rotavirus VP7 in the endoplasmic reticulum. J Cell Biol. 1988;107:1697–1706. doi: 10.1083/jcb.107.5.1697. Of outstanding interest. [DOI] [PMC free article] [PubMed] [Google Scholar]; The rotavirus VP7 is a membrane-associated protein retained in the ER. The authors found 2 separate sequences which are both necessary for retention, although neither alone is sufficient.
  • 9.Machamer C.E., Rose J.K. A specific transmembrane domain of a coronavirus E1 glycoprotein is required for its retention in the golgi region. J Cell Biol. 1987;105:1205–1214. doi: 10.1083/jcb.105.3.1205. Of interest. [DOI] [PMC free article] [PubMed] [Google Scholar]; The coronavirus E1 protein is retained in the Golgi and has 3 membrane-spanning segments. The first domain specifies accumulation in the Golgi.
  • 10.Fausr P.L., Chirgwin J.M., Kornfeld S. Renin, a secretory glycoprotein, acquires phosphomannosyl residues. J Cell Biol. 1987;105:1947–1956. doi: 10.1083/jcb.105.5.1947. Of interest. [DOI] [PMC free article] [PubMed] [Google Scholar]; Renin is a secreted aspartyl protease. When exogenously expressed in Xenopus oocytes or MDCK cells, a fraction of the molecules receive the M-6-P signal. Renin may contain part of the signal for lysosomal protein recognition.
  • 11.Lazarovits J., Roth M. A single amino acid change in the cytoplasmic domain allows the influenza virus hemagglutinin to be endocytosed through coated pits. Cell. 1988;53:743–752. doi: 10.1016/0092-8674(88)90092-x. Of outstanding interest. [DOI] [PubMed] [Google Scholar]; The HA of influenza virus is not normally endocytosed. Putting a tyrosine in the correct position of the 10-amino acid cytoplasmic domain causes it to be endocytosed. Tyrosine can, in some contexts, provide the minimum information for endocytosis.
  • 12.Ahle S., Mann A., Eichelsbacher U., Ungewickell E. Structural relationships between clathrin assembly proteins from the Golgi and the plasma membrane. EMBO J. 1988;7:919–930. doi: 10.1002/j.1460-2075.1988.tb02897.x. Of interest. [DOI] [PMC free article] [PubMed] [Google Scholar]; Clathrin assembly proteins (adaptors) fall into 2 groups, HA1 and HA2. This paper confirms in great detail the earlier results of Robinson and Pearse (J Cell Biol 1986, 102:48–54) that showed that HA1 is specific for the Golgi region, whereas HA2 is found in plasma membrane-derived coated pits and vesicles.
  • 13.Pearse B.M.F. Receptors compete for adaptors found in plasma membrane coated pits. EMBO J. 1988;7:3331–3336. doi: 10.1002/j.1460-2075.1988.tb03204.x. Of interest. [DOI] [PMC free article] [PubMed] [Google Scholar]; Using an affinity chromatography approach, a direct biochemical interaction is revealed between adaptors and the cytoplasmic domains of various membrane receptors. This interaction is weak, but could be effectively multiplied by the binding of a clathrin lattice to many adaptors.
  • 14.Griffiths G., Hoflack B., Simons K., Mellman I., Kornfeld S. The mannose 6-phosphate receptor and the biogenesis of lysosomes. Cell. 1988;52:329–341. doi: 10.1016/s0092-8674(88)80026-6. Of outstanding interest. [DOI] [PubMed] [Google Scholar]; In a quantitative morphological study, the distribution of the M-6-P receptor and a lysosomal glycoprotein were examined. A late endosomal or pre-lysosomal ‘intermediate’ compartment is apparently the site where newly made lysosomal enzymes are sent before reaching the lysosomes.
  • 15.Goda Y., Pfeffer S.R. Selective recycling of the mannose 6-phosphate/IGF-II receptor to the trans Golgi network in vitro. Cell. 1988;55:309–320. doi: 10.1016/0092-8674(88)90054-2. Of interest. [DOI] [PubMed] [Google Scholar]; The M-6-P receptor normally recycles from the intermediate compartment of the TGN. This process has been reconstituted in semi-intact cells.
  • 16.Orci L., Ravazzola M., Amherdt M., Perrelet A., Powell S.K., Quinn D.L., Moore H.P. The trans-most cistemae of the Golgi complex: a compartment for sorting of secretory and plasma membrane proteins. Cell. 1987;51:1039–1051. doi: 10.1016/0092-8674(87)90590-3. Of interest. [DOI] [PubMed] [Google Scholar]; Regulated secretory proteins are segregated from constitutively secreted proteins. In a morphological study, the precise site of sorting was identified as the trans Golgi. Clathrin-coated regions of these cistemae were involved in packaging of insulin into dense granules.
  • 17.Powell S.K., Orci L., Craik C.S., Moore H.-P.H. Efficient targeting to storage granules of human proinsulins with altered propeptide domain. J Cell Biol. 1988;106:1843–1852. doi: 10.1083/jcb.106.6.1843. Of interest. [DOI] [PMC free article] [PubMed] [Google Scholar]; Insulin is normally made as proinsulin, where the C-peptide connects the A- and B-chains. Deleting the entire C-peptide does not alter the sorting of insulin into the regulated pathway, suggesting that the C-peptide is not necessary for expression of the signal for sorting into this pathway.
  • 18.Carroll R.J., Hammer R.E., Chan S.J., Swift H.H., Rubenstein A.H., Steiner D.F. Vol. 85. 1988. A mutant human proinsulin is secrets from islets of Langerthans in increased amounts via an unregulated pathway; pp. 8943–8947. (Proc Natl Acad Sci USA). Of interest. [DOI] [PMC free article] [PubMed] [Google Scholar]; A point mutation in human proinsulin causes 15% of the molecules to be mis-sorted from the regulated pathway into the constitutive pathway. This may be an important clue as to the nature of the sorting signal involved.
  • 19.Chung K.-N., Walter P., Aponte G.W., Moore H.-P.H. Molecular sorting in the secretory pathway. Science. 1989;243:192–197. doi: 10.1126/science.2911732. Of outstanding interest. [DOI] [PubMed] [Google Scholar]; Using affinity chromatography, a group of 25 kD proteins were isolated which bind to proteins secreted by the regulated pathway. These proteins are found in the Golgi region of several cell types. They may be the receptors that direct proteins into the regulated pathway.
  • 20.Urban J., Parczyk K., Leutz A., Kayne M., Kondor-Koch C. Constitutive apical secretion of an 80-kD sulfated glycoproteins complex in the polarized epithelial madin-darby canine kidney cell line. J Cell Biol. 1987;105:2735–2744. doi: 10.1083/jcb.105.6.2735. Of interest. [DOI] [PMC free article] [PubMed] [Google Scholar]; A detailed study of the apical secretion of an endogenous protein in MDCK cells. Inhibition of carbohydrate addition causes random secretion from both surfaces of the cell, suggesting that sugars may be involved in targeting.
  • 21.Caplan M.J., Stow J.I., Newman A.P., Madri J., Anderson H.C., Farquhar M.G., Palade G.E., Jamieson J.D. Dependence on pH of polarized sorting of secreted proteinsNature. 1987;329:632–634. doi: 10.1038/329632a0. Of interest. (Letter to the Editor) [DOI] [PubMed] [Google Scholar]; Weak bases cause basolaterally secreted proteins to be secreted from both surfaces. This may be because of inactivation of an acid-dependent sorting receptor in the TGN, or a non-specific effect on membrane traffic
  • 22.Bennett M.K., Wandinger-Ness A., Simons K. Release of putative exocytic transport vesicles from perforated MDCK cells. EMBO J. 1988;7:4075–4086. doi: 10.1002/j.1460-2075.1988.tb03301.x. Of interest. [DOI] [PMC free article] [PubMed] [Google Scholar]; The authors used a recently developed and powerful technique to study membrane traffic in semi-intact cells. They found that TGN-derived vesicles can be selectively released from these cells.
  • 23.Rindler M.J., Traber M.G. A specific sorting signal is not required for the polarized secretion of newly synthesized proteins from cultured intestinal epithelial cells. J Cell Biol. 1988;107:471–480. doi: 10.1083/jcb.107.2.471. Of interest. [DOI] [PMC free article] [PubMed] [Google Scholar]; Caco2 cells are a useful model system for sorting in intestinal cells. Most soluble proteins are found to be released basolaterally.
  • 24.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;107:13–22. doi: 10.1083/jcb.108.1.13. Of interest. [DOI] [PMC free article] [PubMed] [Google Scholar]; In Caco2 cells, apical membrane proteins and some apically secreted proteins are directly targeted from the TGN. An and-microtubule agent disrupts this delivery.
  • 25.Copeland C.S., Zimmer K.P., Wagner K.R., Healey G.A., Mellman I., Helenius A. Folding trimerization and transport are sequential events in the biogenesis of influenza virus hemagglutinin. Cell. 1988;53:197–209. doi: 10.1016/0092-8674(88)90381-9. Of interest. [DOI] [PubMed] [Google Scholar]; The latest of several papers from this group and the laboratory of Gething and Sambrook that deal with folding of HA Using a variety of techniques, they show that HA passes through 2 intermediate states before reaching the Golgi.
  • 26.Doms R.W., Ruusala A., Machamer C., Helenius J., Helenius A., Rose J.K. Differential effects of mutations in three domains on folding, quatenary structure, and intracellular transport of vesiciular stomatitis virus G protein. J Cell Biol. 1988;107:89–100. doi: 10.1083/jcb.107.1.89. Of interest. [DOI] [PMC free article] [PubMed] [Google Scholar]; Mutations in the ectodomain of the vesicular stomatitis virus G-protein block correct folding, oligomerization and exit from the ER. Mutants in the cytoplasmic domain did not affect folding or oligomerization, but some did affect transport. The cytoplasmic domain may therefore contain a signal for transport.
  • 27.Mostov K.E., Breitfeld P., Harris J.M. An anchor-minus form of the polymeric immunoglobulin receptor is secreted pre-dominantly apically in madin-darby canine kidney cells. J Cell Biol. 1987;105:2031–2036. doi: 10.1083/jcb.105.5.2031. Of outstanding interest. [DOI] [PMC free article] [PubMed] [Google Scholar]; The pIg receptor is a useful model system for studying protein sorting in polarized cells. Truncating the membrane-anchored form yields a soluble protein that is secreted apically. This suggest that the signals for apical targeting of membrane and soluble proteins may be related.
  • 28.Lisanti M.P., Sargiacomo M., Graeve I., Saltiel A.R., Rodriguez-Boulan E. Vol. 85. 1988. Polarized apical distribution of glycosyl phosphotidylinositol-anchored proteins in a renal epithelial cell line; pp. 9557–9561. (Proc Natl Acad Sci). Of outstanding interest. [DOI] [PMC free article] [PubMed] [Google Scholar]; A recently discovered class of membrane proteins do not have a polypeptide that spans the membrane, but instead are anchored by a glycolipid. This study shows that all of these proteins on the surface of MDCK cells are on the apical surface. The glycolipid anchor may contain a sorting signal.
  • 29.Simister N.E., Mostov K.E. An Fc receptor structurally related to MHC class I antigensNature. 1989;337:184–186. doi: 10.1038/337184a0. Of oustanding interest. (Letter to the Editor) [DOI] [PubMed] [Google Scholar]; In the small intestines of newborn rats, an Fc receptor binds IgG in the lumen and transports the IgG from the apical to the basolateral surface. This trancytosis is in the opposite direction from the pig receptor. The receptor has 2 chains and is highly homologous to major histocompatibility complex class I antigens. The cytoplasmic domain lacks a tyrosine for endocytosis, but contains a tryptophan and a phenylalanine, which might act as substitutes.

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