Acidic Di-leucine Motif Essential for AP-3-dependent Sorting and Restriction of the Functional Specificity of the Vam3p Vacuolar t-SNARE

doi:10.1083/jcb.142.4.913

This Article

	Full Text
	Full Text (PDF, 1760K)
	PPT slides of all figures
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Darsow, T.
	Articles by Emr, S. D.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Darsow, T.
	Articles by Emr, S. D.


Social Bookmarking

	What's this?

© The Rockefeller University Press, 0021-9525/1998//913 $5.00
The Journal of Cell Biology, Volume 142, Number 4, , 1998 913-922

Articles

Acidic Di-leucine Motif Essential for AP-3–dependent Sorting and Restriction of the Functional Specificity of the Vam3p Vacuolar t-SNARE

Tamara Darsow, Christopher G. Burd, and Scott D. Emr

Division of Cellular and Molecular Medicine and Department of Biology, Howard Hughes Medical Institute, University of California, San Diego, School of Medicine, La Jolla, California 92093-0668

The transport of newly synthesized proteins through the vacuolarprotein sorting pathway in the budding yeast Saccharomycescerevisiae requires two distinct target SNAP receptor (t-SNARE)proteins, Pep12p and Vam3p. Pep12p is localized to the pre-vacuolarendosome and its activity is required for transport of proteinsfrom the Golgi to the vacuole through a well defined route,the carboxypeptidase Y (CPY) pathway. Vam3p is localized tothe vacuole where it mediates delivery of cargoes from boththe CPY and the recently described alkaline phosphatase (ALP)pathways. Surprisingly, despite their organelle-specific functionsin sorting of vacuolar proteins, overexpression of VAM3 cansuppress the protein sorting defects of pep12 ${Delta}$ cells. Basedon this observation, we developed a genetic screen to identifydomains in Vam3p (e.g., localization and/or specific protein–proteininteraction domains) that allow it to efficiently substitutefor Pep12p. Using this screen, we identified mutations in a7–amino acid sequence in Vam3p that lead to missortingof Vam3p from the ALP pathway into the CPY pathway where it can substitute for Pep12p at the pre-vacuolar endosome. Thisregion contains an acidic di-leucine sequence that is closelyrelated to sorting signals required for AP-3 adaptor–dependenttransport in both yeast and mammalian systems. Furthermore,disruption of AP-3 function also results in the ability ofwild-type Vam3p to compensate for pep12 mutants, suggesting that AP-3 mediates the sorting of Vam3p via the di-leucinesignal. Together, these data provide the first identificationof an adaptor protein–specific sorting signal in a t-SNAREprotein, and suggest that AP-3–dependent sorting of Vam3pacts to restrict its interaction with compartment-specificaccessory proteins, thereby regulating its function. Regulatedtransport of cargoes such as Vam3p through the AP-3–dependentpathway may play an important role in maintaining the unique composition, function, and morphology of the vacuole.

Key Words: vacuole • SNARE • di-leucine • Saccharomyces cerevisiae • AP-3

Abbreviations used in this paper: ALP, alkaline phosphatase; CPY, carboxypeptidase Y; GFP, green fluorescent protein; NSF, N-ethylmaleimide–sensitive factor; ORF, open reading frame; SNAP, soluble NSF attachment protein; SNARE, SNAP receptor; VPS, vacuolar protein sorting.

Address all correspondence to Scott D. Emr, Division of Cellularand Molecular Medicine and Department of Biology, Howard HughesMedical Institute, University of California, San Diego, LaJolla, CA 92093-0668. Tel.: (619) 534-6462. Fax: (619) 534-6414.E-mail: semr{at}ucsd.edu

CiteULike

Complore

Connotea

Del.icio.us Add to Digg

Digg

Facebook

Technorati

Twitter What's this?

This article has been cited by other articles:

Angers, C. G., Merz, A. J. (2009). HOPS Interacts with Apl5 at the Vacuole Membrane and Is Required for Consumption of AP-3 Transport Vesicles. Mol. Biol. Cell 20: 4563-4574 [Abstract] [Full Text]
Pokrzywa, W., Guerriat, B., Dodzian, J., Morsomme, P. (2009). Dual Sorting of the Saccharomyces cerevisiae Vacuolar Protein Sna4p. Eukaryot Cell 8: 278-286 [Abstract] [Full Text]
Anand, V. C., Daboussi, L., Lorenz, T. C., Payne, G. S. (2009). Genome-wide Analysis of AP-3-dependent Protein Transport in Yeast. Mol. Biol. Cell 20: 1592-1604 [Abstract] [Full Text]
Morishita, M., Engebrecht, J. (2008). Sorting Signals within the Saccharomyces cerevisiae Sporulation-Specific Dityrosine Transporter, Dtr1p, C Terminus Promote Golgi-to-Prospore Membrane Transport. Eukaryot Cell 7: 1674-1684 [Abstract] [Full Text]
Rozenfeld, R., Devi, L. A. (2008). Regulation of CB1 cannabinoid receptor trafficking by the adaptor protein AP-3. FASEB J. 22: 2311-2322 [Abstract] [Full Text]
Besteiro, S., Tonn, D., Tetley, L., Coombs, G. H., Mottram, J. C. (2008). The AP3 adaptor is involved in the transport of membrane proteins to acidocalcisomes of Leishmania. J. Cell Sci. 121: 561-570 [Abstract] [Full Text]
Chidambaram, S., Zimmermann, J., von Mollard, G. F. (2008). ENTH domain proteins are cargo adaptors for multiple SNARE proteins at the TGN endosome. J. Cell Sci. 121: 329-338 [Abstract] [Full Text]
Jain, P., Mostoller, K., Flaig, K. E., Ahuja, J., Lepoutre, V., Alefantis, T., Khan, Z. K., Wigdahl, B. (2007). Identification of Human T Cell Leukemia Virus Type 1 Tax Amino Acid Signals and Cellular Factors Involved in Secretion of the Viral Oncoprotein. J. Biol. Chem. 282: 34581-34593 [Abstract] [Full Text]
Noviello, C. M., Pond, S. L. K., Lewis, M. J., Richman, D. D., Pillai, S. K., Yang, O. O., Little, S. J., Smith, D. M., Guatelli, J. C. (2007). Maintenance of Nef-Mediated Modulation of Major Histocompatibility Complex Class I and CD4 after Sexual Transmission of Human Immunodeficiency Virus Type 1. J. Virol. 81: 4776-4786 [Abstract] [Full Text]
Wen, W., Chen, L., Wu, H., Sun, X., Zhang, M., Banfield, D. K. (2006). Identification of the Yeast R-SNARE Nyv1p as a Novel Longin Domain-containing Protein. Mol. Biol. Cell 17: 4282-4299 [Abstract] [Full Text]
Coleman, S. H., Madrid, R., Van Damme, N., Mitchell, R. S., Bouchet, J., Servant, C., Pillai, S., Benichou, S., Guatelli, J. C. (2006). Modulation of Cellular Protein Trafficking by Human Immunodeficiency Virus Type 1 Nef: Role of the Acidic Residue in the ExxxLL Motif. J. Virol. 80: 1837-1849 [Abstract] [Full Text]
Shoji, J.-y., Arioka, M., Kitamoto, K. (2006). Vacuolar Membrane Dynamics in the Filamentous Fungus Aspergillus oryzae. Eukaryot Cell 5: 411-421 [Abstract] [Full Text]
Styers, M. L., Salazar, G., Love, R., Peden, A. A., Kowalczyk, A. P., Faundez, V. (2004). The Endo-Lysosomal Sorting Machinery Interacts with the Intermediate Filament Cytoskeleton. Mol. Biol. Cell 15: 5369-5382 [Abstract] [Full Text]
Bruinsma, P., Spelbrink, R. G., Nothwehr, S. F. (2004). Retrograde Transport of the Mannosyltransferase Och1p to the Early Golgi Requires a Component of the COG Transport Complex. J. Biol. Chem. 279: 39814-39823 [Abstract] [Full Text]
Kim, M.-H., Hersh, L. B. (2004). The Vesicular Acetylcholine Transporter Interacts with Clathrin-associated Adaptor Complexes AP-1 and AP-2. J. Biol. Chem. 279: 12580-12587 [Abstract] [Full Text]
Fernandez-Salas, E., Steward, L. E., Ho, H., Garay, P. E., Sun, S. W., Gilmore, M. A., Ordas, J. V., Wang, J., Francis, J., Aoki, K. R. (2004). Plasma membrane localization signals in the light chain of botulinum neurotoxin. Proc. Natl. Acad. Sci. USA 101: 3208-3213 [Abstract] [Full Text]
Sun, B., Chen, L., Cao, W., Roth, A. F., Davis, N. G. (2004). The Yeast Casein Kinase Yck3p Is Palmitoylated, then Sorted to the Vacuolar Membrane with AP-3-dependent Recognition of a YXX{phi} Adaptin Sorting Signal. Mol. Biol. Cell 15: 1397-1406 [Abstract] [Full Text]
Chidambaram, S., Mullers, N., Wiederhold, K., Haucke, V., von Mollard, G. F. (2004). Specific Interaction between SNAREs and Epsin N-terminal Homology (ENTH) Domains of Epsin-related Proteins in trans-Golgi Network to Endosome Transport. J. Biol. Chem. 279: 4175-4179 [Abstract] [Full Text]
Martinez-Arca, S., Rudge, R., Vacca, M., Raposo, G., Camonis, J., Proux-Gillardeaux, V., Daviet, L., Formstecher, E., Hamburger, A., Filippini, F., D'Esposito, M., Galli, T. (2003). A dual mechanism controlling the localization and function of exocytic v-SNAREs. Proc. Natl. Acad. Sci. USA 100: 9011-9016 [Abstract] [Full Text]
Rohde, J., Dietrich, L., Langosch, D., Ungermann, C. (2003). The Transmembrane Domain of Vam3 Affects the Composition of cis- and trans-SNARE Complexes to Promote Homotypic Vacuole Fusion. J. Biol. Chem. 278: 1656-1662 [Abstract] [Full Text]
Rodionov, D. G., Honing, S., Silye, A., Kongsvik, T. L., von Figura, K., Bakke, O. (2002). Structural Requirements for Interactions between Leucine-sorting Signals and Clathrin-associated Adaptor Protein Complex AP3. J. Biol. Chem. 277: 47436-47443 [Abstract] [Full Text]
Desmoucelles, C., Pinson, B., Saint-Marc, C., Daignan-Fornier, B. (2002). Screening the Yeast "Disruptome" for Mutants Affecting Resistance to the Immunosuppressive Drug, Mycophenolic Acid. J. Biol. Chem. 277: 27036-27044 [Abstract] [Full Text]
Bonangelino, C. J., Chavez, E. M., Bonifacino, J. S. (2002). Genomic Screen for Vacuolar Protein Sorting Genes in Saccharomyces cerevisiae. Mol. Biol. Cell 13: 2486-2501 [Abstract] [Full Text]
Nishimura, N., Plutner, H., Hahn, K., Balch, W. E. (2002). The delta subunit of AP-3 is required for efficient transport of VSV-G from the trans-Golgi network to the cell surface. Proc. Natl. Acad. Sci. USA 99: 6755-6760 [Abstract] [Full Text]
Volker, A., Stierhof, Y.-D., Jurgens, G. (2002). Cell cycle-independent expression of the Arabidopsis cytokinesis-specific syntaxin KNOLLE results in mistargeting to the plasma membrane and is not sufficient for cytokinesis. J. Cell Sci. 114: 3001-3012 [Abstract] [Full Text]
Seeley, E. S., Kato, M., Margolis, N., Wickner, W., Eitzen, G. (2002). Genomic Analysis of Homotypic Vacuole Fusion. Mol. Biol. Cell 13: 782-794 [Abstract] [Full Text]
Laage, R., Ungermann, C. (2001). The N-terminal Domain of the t-SNARE Vam3p Coordinates Priming and Docking in Yeast Vacuole Fusion. Mol. Biol. Cell 12: 3375-3385 [Abstract] [Full Text]
Huizing, M., Sarangarajan, R., Strovel, E., Zhao, Y., Gahl, W. A., Boissy, R. E. (2001). AP-3 Mediates Tyrosinase but Not TRP-1 Trafficking in Human Melanocytes. Mol. Biol. Cell 12: 2075-2085 [Abstract] [Full Text]
Deloche, O., Yeung, B. G., Payne, G. S., Schekman, R. (2001). Vps10p Transport from the trans-Golgi Network to the Endosome Is Mediated by Clathrin-coated Vesicles. Mol. Biol. Cell 12: 475-485 [Abstract] [Full Text]
Kasai, K., Akagawa, K. (2001). Roles of the cytoplasmic and transmembrane domains of syntaxins in intracellular localization and trafficking. J. Cell Sci. 114: 3115-3124 [Abstract] [Full Text]
Le Borgne, R., Planque, N., Martin, P., Dewitte, F., Saule, S., Hoflack, B. (2001). The AP-3-dependent targeting of the melanosomal glycoprotein QNR-71 requires a di-leucine-based sorting signal. J. Cell Sci. 114: 2831-2841 [Abstract] [Full Text]
Darsow, T., Katzmann, D. J., Cowles, C. R., Emr, S. D. (2001). Vps41p Function in the Alkaline Phosphatase Pathway Requires Homo-oligomerization and Interaction with AP-3 through Two Distinct Domains. Mol. Biol. Cell 12: 37-51 [Abstract] [Full Text]
Drake, M. T., Zhu, Y., Kornfeld, S. (2000). The Assembly of AP-3 Adaptor Complex-containing Clathrin-coated Vesicles on Synthetic Liposomes. Mol. Biol. Cell 11: 3723-3736 [Abstract] [Full Text]
Reggiori, F., Black, M. W., Pelham, H. R. B. (2000). Polar Transmembrane Domains Target Proteins to the Interior of the Yeast Vacuole. Mol. Biol. Cell 11: 3737-3749 [Abstract] [Full Text]
Yang, W, Li, C, Ward, D., Kaplan, J, Mansour, S. (2000). Defective organellar membrane protein trafficking in Ap3b1-deficient cells. J. Cell Sci. 113: 4077-4086 [Abstract]
Rohn, W., Rouille, Y, Waguri, S, Hoflack, B (2000). Bi-directional trafficking between the trans-Golgi network and the endosomal/lysosomal system. J. Cell Sci. 113: 2093-2101 [Abstract]
Sanderfoot, A. A., Kovaleva, V., Zheng, H., Raikhel, N. V. (1999). The t-SNARE AtVAM3p Resides on the Prevacuolar Compartment in Arabidopsis Root Cells. Plant Physiol. 121: 929-938 [Abstract] [Full Text]
Zhen, L., Jiang, S., Feng, L., Bright, N. A., Peden, A. A., Seymour, A. B., Novak, E. K., Elliott, R., Gorin, M. B., Robinson, M. S., Swank, R. T. (1999). Abnormal Expression and Subcellular Distribution of Subunit Proteins of the AP-3 Adaptor Complex Lead to Platelet Storage Pool Deficiency in the Pearl Mouse. Blood 94: 146-155 [Abstract] [Full Text]
Calvo, P. A., Frank, D. W., Bieler, B. M., Berson, J. F., Marks, M. S. (1999). A Cytoplasmic Sequence in Human Tyrosinase Defines a Second Class of Di-leucine-based Sorting Signals for Late Endosomal and Lysosomal Delivery. J. Biol. Chem. 274: 12780-12789 [Abstract] [Full Text]
Pitcher, C., Höning, S., Fingerhut, A., Bowers, K., Marsh, M. (1999). Cluster of Differentiation Antigen 4�() Endocytosis and Adaptor Complex Binding Require Activation of the Endocytosis Signal by Serine Phosphorylation. Mol. Biol. Cell 10: 677-691 [Abstract] [Full Text]
Yang, B., Gonzalez, L. Jr., Prekeris, R., Steegmaier, M., Advani, R. J., Scheller, R. H. (1999). SNARE Interactions Are Not Selective. IMPLICATIONS FOR MEMBRANE FUSION SPECIFICITY. J. Biol. Chem. 274: 5649-5653 [Abstract] [Full Text]
Wong, S. H., Xu, Y., Zhang, T., Griffiths, G., Lowe, S. L., Subramaniam, V. N., Seow, K. T., Hong, W. (1999). GS32, a Novel Golgi SNARE of 32�kDa, Interacts Preferentially with Syntaxin 6. Mol. Biol. Cell 10: 119-134 [Abstract] [Full Text]
Vickers, M. F., Yao, S. Y. M., Baldwin, S. A., Young, J. D., Cass, C. E. (2000). Nucleoside Transporter Proteins of Saccharomyces cerevisiae. DEMONSTRATION OF A TRANSPORTER (FUI1) WITH HIGH URIDINE SELECTIVITY IN PLASMA MEMBRANES AND A TRANSPORTER (FUN26) WITH BROAD NUCLEOSIDE SELECTIVITY IN INTRACELLULAR MEMBRANES. J. Biol. Chem. 275: 25931-25938 [Abstract] [Full Text]
Storch, S., Braulke, T. (2001). Multiple C-terminal Motifs of the 46-kDa Mannose 6-Phosphate Receptor Tail Contribute to Efficient Binding of Medium Chains of AP-2 and AP-3. J. Biol. Chem. 276: 4298-4303 [Abstract] [Full Text]
Sandoval, I. V., Martinez-Arca, S., Valdueza, J., Palacios, S., Holman, G. D. (2000). Distinct Reading of Different Structural Determinants Modulates the Dileucine-mediated Transport Steps of the Lysosomal Membrane Protein LIMPII and the Insulin-sensitive Glucose Transporter GLUT4. J. Biol. Chem. 275: 39874-39885 [Abstract] [Full Text]
Bogdanovic, A., Bruckert, F., Morio, T., Satre, M. (2000). A Syntaxin 7 Homologue Is Present in Dictyostelium discoideum Endosomes and Controls Their Homotypic Fusion. J. Biol. Chem. 275: 36691-36697 [Abstract] [Full Text]
Wehrle-Haller, B., Imhof, B. A. (2001). Stem Cell Factor Presentation to c-Kit. IDENTIFICATION OF A BASOLATERAL TARGETING DOMAIN. J. Biol. Chem. 276: 12667-12674 [Abstract] [Full Text]
Peden, A. A., Park, G. Y., Scheller, R. H. (2001). The Di-leucine Motif of Vesicle-associated Membrane Protein 4 Is Required for Its Localization and AP-1 Binding. J. Biol. Chem. 276: 49183-49187 [Abstract] [Full Text]