Home LiteratureArticle Details
PMID: 9265642 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Novel genes involved in endosomal traffic in yeast revealed by suppression of a targeting-defective plasma membrane ATPase mutant.

The Journal of cell biology ·Vol. 138 ·No. 4 ·1997-08-25 ·Pages 731-46

Luo Wj, Chang A

Abstract

A novel genetic selection was used to identify genes regulating traffic in the yeast endosomal system. We took advantage of a temperature-sensitive mutant in PMA1, encoding the plasma membrane ATPase, in which newly synthesized Pma1 is mislocalized to the vacuole via the endosome. Diversion of mutant Pma1 from vacuolar delivery and rerouting to the plasma membrane is a major mechanism of suppression of pma1(ts). 16 independent suppressor of pma1 (sop) mutants were isolated. Identification of the corresponding genes reveals eight that are identical with VPS genes required for delivery of newly synthesized vacuolar proteins. A second group of SOP genes participates in vacuolar delivery of mutant Pma1 but is not essential for delivery of the vacuolar protease carboxypeptidase Y. Because the biosynthetic pathway to the vacuole intersects with the endocytic pathway, internalization of a bulk membrane endocytic marker FM 4-64 was assayed in the sop mutants. By this means, defective endosome-to-vacuole trafficking was revealed in a subset of sop mutants. Another subset of sop mutants displays perturbed trafficking between endosome and Golgi: impaired pro-alpha factor processing in these strains was found to be due to defective recycling of the trans-Golgi protease Kex2. One of these strains defective in Kex2 trafficking carries a mutation in SOP2, encoding a homologue of mammalian synaptojanin (implicated in synaptic vesicle endocytosis and recycling). Thus, cell surface delivery of mutant Pma1 can occur as a consequence of disturbances at several different sites in the endosomal system.

MeSH Terms
Biological Transport/genetics Biomarkers Carrier Proteins/genetics Cell Membrane/enzymology,genetics,metabolism Endosomes/enzymology,genetics,metabolism Fungal Proteins/genetics Intracellular Membranes/enzymology Mating Factor Mutagenesis Nerve Tissue Proteins/genetics Peptides/genetics Phosphoric Monoester Hydrolases/genetics Proprotein Convertases Protein Processing, Post-Translational Proton-Translocating ATPases/genetics Receptors, Cell Surface/genetics Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Subtilisins/metabolism Vacuoles/chemistry,enzymology,genetics Vesicular Transport Proteins
Chemicals
Biomarkers Carrier Proteins Fungal Proteins Nerve Tissue Proteins PEP1 protein, S cerevisiae PMA2 protein, S cerevisiae Peptides Receptors, Cell Surface Saccharomyces cerevisiae Proteins Vesicular Transport Proteins Mating Factor synaptojanin Phosphoric Monoester Hydrolases Proprotein Convertases Subtilisins KEX2 protein, S cerevisiae PMA1 protein, S cerevisiae Proton-Translocating ATPases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Luo W j
Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Chang A
References (75)
75 references, click to expand
  1. A putative GTP binding protein homologous to interferon-inducible Mx proteins performs an essential function in yeast protein sorting.
    Cell. 1990 Jun 15;61(6):1063-74 PMID: 2112425
  2. Phosphoinositides as regulators in membrane traffic.
    Science. 1996 Mar 15;271(5255):1533-9 PMID: 8599109
  3. Clathrin: a role in the intracellular retention of a Golgi membrane protein.
    Science. 1989 Sep 22;245(4924):1358-65 PMID: 2675311
  4. Methods for studying the yeast vacuole.
    Methods Enzymol. 1991;194:644-61 PMID: 1706462
  5. Improved method for high efficiency transformation of intact yeast cells.
    Nucleic Acids Res. 1992 Mar 25;20(6):1425 PMID: 1561104
  6. Allele-specific suppression of a defective trans-Golgi network (TGN) localization signal in Kex2p identifies three genes involved in localization of TGN transmembrane proteins.
    Mol Cell Biol. 1996 Nov;16(11):6208-17 PMID: 8887651
  7. The requirement for yeast superoxide dismutase is bypassed through mutations in BSD2, a novel metal homeostasis gene.
    Mol Cell Biol. 1994 Nov;14(11):7037-45 PMID: 7935419
  8. Phospholipid transfer activity is relevant to but not sufficient for the essential function of the yeast SEC14 gene product.
    EMBO J. 1993 Dec;12(12):4775-84 PMID: 8223486
  9. Intracellular trafficking of lysosomal membrane proteins.
    Bioessays. 1996 May;18(5):379-89 PMID: 8639161
  10. Endosome to Golgi retrieval of the vacuolar protein sorting receptor, Vps10p, requires the function of the VPS29, VPS30, and VPS35 gene products.
    J Cell Biol. 1997 Apr 7;137(1):79-92 PMID: 9105038
  11. Mutation of a tyrosine localization signal in the cytosolic tail of yeast Kex2 protease disrupts Golgi retention and results in default transport to the vacuole.
    Mol Biol Cell. 1992 Dec;3(12):1353-71 PMID: 1493334
  12. Yeast Ypt51p and mammalian Rab5: counterparts with similar function in the early endocytic pathway.
    J Cell Sci. 1995 Nov;108 ( Pt 11):3509-21 PMID: 8586662
  13. Endocytosis without clathrin.
    Trends Cell Biol. 1994 Aug;4(8):275-7 PMID: 14731589
  14. Genetic and biochemical studies of protein sorting to the yeast vacuole.
    Curr Opin Cell Biol. 1993 Aug;5(4):641-6 PMID: 8257606
  15. Yeast vacuolar proenzymes are sorted in the late Golgi complex and transported to the vacuole via a prevacuolar endosome-like compartment.
    J Cell Biol. 1993 Jun;121(6):1245-56 PMID: 8509446
  16. The biogenesis of lysosomes.
    Annu Rev Cell Biol. 1989;5:483-525 PMID: 2557062
  17. Building a multichain receptor: synthesis, degradation, and assembly of the T-cell antigen receptor.
    Proc Natl Acad Sci U S A. 1987 May;84(9):2688-92 PMID: 3495001
  18. Partial purification and characterization of early and late endosomes from yeast. Identification of four novel proteins.
    J Biol Chem. 1993 Jul 5;268(19):14376-86 PMID: 8314797
  19. Substitutions in the hydrophobic core of the alpha-factor receptor of Saccharomyces cerevisiae permit response to Saccharomyces kluyveri alpha-factor and to antagonist.
    Mol Cell Biol. 1992 Sep;12(9):3959-66 PMID: 1324410
  20. The Saccharomyces cerevisiae MVP1 gene interacts with VPS1 and is required for vacuolar protein sorting.
    Mol Cell Biol. 1995 Mar;15(3):1671-8 PMID: 7862158
  21. Beta-D-fructofuranoside fructohydrolase from yeast.
    Methods Enzymol. 1975;42:504-11 PMID: 237205
  22. The sorting receptor for yeast vacuolar carboxypeptidase Y is encoded by the VPS10 gene.
    Cell. 1994 May 20;77(4):579-86 PMID: 8187177
  23. Half-life of the plasma membrane ATPase and its activating system in resting yeast cells.
    Biochim Biophys Acta. 1991 Apr 2;1063(2):265-8 PMID: 1826456
  24. The Lowe's oculocerebrorenal syndrome gene encodes a protein highly homologous to inositol polyphosphate-5-phosphatase.
    Nature. 1992 Jul 16;358(6383):239-42 PMID: 1321346
  25. Novel Golgi to vacuole delivery pathway in yeast: identification of a sorting determinant and required transport component.
    EMBO J. 1997 May 15;16(10):2769-82 PMID: 9184222
  26. A presynaptic inositol-5-phosphatase.
    Nature. 1996 Jan 25;379(6563):353-7 PMID: 8552192
  27. Signal-mediated retrieval of a membrane protein from the Golgi to the ER in yeast.
    J Cell Biol. 1994 Nov;127(3):653-65 PMID: 7962050
  28. Molecular mechanisms in synaptic vesicle endocytosis and recycling.
    Neuron. 1996 Mar;16(3):481-6 PMID: 8785046
  29. Lysosomal sorting mutants of coronavirus E1 protein, a Golgi membrane protein.
    J Cell Sci. 1990 Feb;95 ( Pt 2):191-7 PMID: 2164517
  30. Three proteolytic systems in the yeast saccharomyces cerevisiae.
    J Biol Chem. 1991 May 5;266(13):7963-6 PMID: 2022624
  31. Oligomerization and intracellular protein transport: dimerization of intestinal dipeptidylpeptidase IV occurs in the Golgi apparatus.
    Biochemistry. 1991 Feb 19;30(7):1908-15 PMID: 1671557
  32. Endocytosis is required for the growth of vacuolar H(+)-ATPase-defective yeast: identification of six new END genes.
    J Cell Biol. 1994 Oct;127(2):373-86 PMID: 7929582
  33. Protein sorting in yeast: mutants defective in vacuole biogenesis mislocalize vacuolar proteins into the late secretory pathway.
    Cell. 1986 Dec 26;47(6):1041-51 PMID: 3536126
  34. A new vital stain for visualizing vacuolar membrane dynamics and endocytosis in yeast.
    J Cell Biol. 1995 Mar;128(5):779-92 PMID: 7533169
  35. Large-scale analysis of gene expression, protein localization, and gene disruption in Saccharomyces cerevisiae.
    Genes Dev. 1994 May 1;8(9):1087-105 PMID: 7926789
  36. Cis- and trans-acting functions required for endocytosis of the yeast pheromone receptors.
    J Cell Biol. 1993 Jul;122(1):53-65 PMID: 8391002
  37. Protein sorting by transport vesicles.
    Science. 1996 Apr 12;272(5259):227-34 PMID: 8602507
  38. Membrane transport in the endocytic pathway.
    Curr Opin Cell Biol. 1995 Aug;7(4):552-63 PMID: 7495576
  39. Assay of yeast mating reaction.
    Methods Enzymol. 1991;194:77-93 PMID: 2005823
  40. Targeting of the yeast plasma membrane [H+]ATPase: a novel gene AST1 prevents mislocalization of mutant ATPase to the vacuole.
    J Cell Biol. 1995 Jan;128(1-2):39-49 PMID: 7822420
  41. Transport through the yeast endocytic pathway occurs through morphologically distinct compartments and requires an active secretory pathway and Sec18p/N-ethylmaleimide-sensitive fusion protein.
    Mol Biol Cell. 1997 Jan;8(1):13-31 PMID: 9017592
  42. Vps10p cycles between the late-Golgi and prevacuolar compartments in its function as the sorting receptor for multiple yeast vacuolar hydrolases.
    J Cell Biol. 1996 May;133(3):529-41 PMID: 8636229
  43. Basic local alignment search tool.
    J Mol Biol. 1990 Oct 5;215(3):403-10 PMID: 2231712
  44. Sorting of membrane proteins in the yeast secretory pathway.
    J Biol Chem. 1994 Apr 8;269(14):10185-8 PMID: 8144594
  45. Maturation of the yeast plasma membrane [H+]ATPase involves phosphorylation during intracellular transport.
    J Cell Biol. 1991 Oct;115(2):289-95 PMID: 1833410
  46. Protein sorting in Saccharomyces cerevisiae: isolation of mutants defective in the delivery and processing of multiple vacuolar hydrolases.
    Mol Cell Biol. 1988 Nov;8(11):4936-48 PMID: 3062374
  47. Proteinase mutants of Saccharomyces cerevisiae.
    Genetics. 1977 Jan;85(1):23-33 PMID: 320092
  48. Morphological classification of the yeast vacuolar protein sorting mutants: evidence for a prevacuolar compartment in class E vps mutants.
    Mol Biol Cell. 1992 Dec;3(12):1389-402 PMID: 1493335
  49. Yeast Kex1p is a Golgi-associated membrane protein: deletions in a cytoplasmic targeting domain result in mislocalization to the vacuolar membrane.
    J Cell Biol. 1992 Dec;119(6):1459-68 PMID: 1469044
  50. Endocytosis in yeast: evidence for the involvement of a small GTP-binding protein (Ypt7p).
    Cell. 1992 Dec 24;71(7):1131-42 PMID: 1473149
  51. Inositols do it all.
    Genes Dev. 1996 May 1;10(9):1051-3 PMID: 8654921
  52. Alternative pathways for the sorting of soluble vacuolar proteins in yeast: a vps35 null mutant missorts and secretes only a subset of vacuolar hydrolases.
    Mol Biol Cell. 1992 Apr;3(4):415-27 PMID: 1498362
  53. Enzymes required for yeast prohormone processing.
    Annu Rev Physiol. 1988;50:345-62 PMID: 3288097
  54. The newly identified yeast GRD genes are required for retention of late-Golgi membrane proteins.
    Mol Cell Biol. 1996 Jun;16(6):2700-7 PMID: 8649377
  55. Quality control in the secretory pathway.
    Curr Opin Cell Biol. 1995 Aug;7(4):523-9 PMID: 7495572
  56. A role for clathrin in the sorting of vacuolar proteins in the Golgi complex of yeast.
    EMBO J. 1992 Aug;11(8):2811-8 PMID: 1639056
  57. Signal transduction and membrane traffic: the PITP/phosphoinositide connection.
    Cell. 1995 Jun 2;81(5):659-62 PMID: 7774006
  58. Involvement of Ypt7p, a small GTPase, in traffic from late endosome to the vacuole in yeast.
    J Cell Sci. 1993 Nov;106 ( Pt 3):823-30 PMID: 8308065
  59. p145, a major Grb2-binding protein in brain, is co-localized with dynamin in nerve terminals where it undergoes activity-dependent dephosphorylation.
    J Biol Chem. 1994 Dec 2;269(48):30132-9 PMID: 7982917
  60. Receptor-mediated protein sorting to the vacuole in yeast: roles for a protein kinase, a lipid kinase and GTP-binding proteins.
    Annu Rev Cell Dev Biol. 1995;11:1-33 PMID: 8689553
  61. VPS27 controls vacuolar and endocytic traffic through a prevacuolar compartment in Saccharomyces cerevisiae.
    J Cell Biol. 1995 Nov;131(3):603-17 PMID: 7593183
  62. Hepatitis B surface antigen assembles in a post-ER, pre-Golgi compartment.
    J Cell Biol. 1992 Sep;118(6):1305-20 PMID: 1522109
  63. Multisubunit assembly of an integral plasma membrane channel protein, gap junction connexin43, occurs after exit from the ER.
    Cell. 1993 Sep 24;74(6):1065-77 PMID: 7691412
  64. Vps1p, a member of the dynamin GTPase family, is necessary for Golgi membrane protein retention in Saccharomyces cerevisiae.
    EMBO J. 1993 Aug;12(8):3049-59 PMID: 8344247
  65. New phenotype of mutations deficient in glucosylation of the lipid-linked oligosaccharide: cloning of the ALG8 locus.
    Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5977-81 PMID: 8016100
  66. The cytoplasmic tail domain of the vacuolar protein sorting receptor Vps10p and a subset of VPS gene products regulate receptor stability, function, and localization.
    Mol Biol Cell. 1995 Sep;6(9):1089-102 PMID: 8534908
  67. Cell biology of von Willebrand factor.
    Annu Rev Cell Biol. 1990;6:217-46 PMID: 2275814
  68. Membrane protein retention in the yeast Golgi apparatus: dipeptidyl aminopeptidase A is retained by a cytoplasmic signal containing aromatic residues.
    J Cell Biol. 1993 Jun;121(6):1197-209 PMID: 8509444
  69. Golgi and vacuolar membrane proteins reach the vacuole in vps1 mutant yeast cells via the plasma membrane.
    J Cell Biol. 1995 Apr;129(1):35-46 PMID: 7698993
  70. Coat proteins and vesicle budding.
    Science. 1996 Mar 15;271(5255):1526-33 PMID: 8599108
  71. Intracellular aspects of the process of protein synthesis.
    Science. 1975 Aug 1;189(4200):347-58 PMID: 1096303
  72. Distinct sequence determinants direct intracellular sorting and modification of a yeast vacuolar protease.
    Cell. 1987 Mar 13;48(5):875-85 PMID: 3028648
  73. A pathway for targeting soluble misfolded proteins to the yeast vacuole.
    J Cell Biol. 1996 Nov;135(3):623-33 PMID: 8909538
  74. Multilamellar endosome-like compartment accumulates in the yeast vps28 vacuolar protein sorting mutant.
    Mol Biol Cell. 1996 Jun;7(6):985-99 PMID: 8817003
  75. Predicting coiled coils from protein sequences.
    Science. 1991 May 24;252(5009):1162-4 PMID: 2031185
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
Published
1997-08-25
Pages
731-46
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2138039
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]