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Gene Review

VPS45  -  Vps45p

Saccharomyces cerevisiae S288c

Synonyms: STT10, VPL28, Vacuolar protein sorting-associated protein 45, YGL095C
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High impact information on VPS45

  • The SM protein Vps45p binds its Sx Tlg2p in a manner analogous to that captured by the Sly1p-Sed5p crystal structure, whereby the NH2-terminal peptide of the Sx inserts into a hydrophobic pocket on the outer face of domain I of the SM protein [1].
  • These complexes are clearly different from those found in either wild-type or sec18-1 cells as the Sec1p/Munc18 (SM) protein Vps45p does not bind to them [2].
  • The Sec1p/Munc18 (SM) protein, Vps45p, cycles on and off membranes during vesicle transport [2].
  • Studies of the yeast trans-Golgi network (TGN)/endosomal SNARE complex, which includes the syntaxin-like SNARE Tlg2p, have suggested that its assembly requires activation by binding of the SM protein Vps45p to the cytoplasmic region of Tlg2p folded into a closed conformation [3].
  • In this study we demonstrate that, whereas VPS45 and VPS27 are required for the vacuolar delivery of several membrane proteins, the vacuolar membrane protein alkaline phosphatase (ALP) reaches its final destination without the function of these two genes [4].

Biological context of VPS45

  • Mutations in the VPS45 gene, a SEC1 homologue, result in vacuolar protein sorting defects and accumulation of membrane vesicles [5].
  • This analysis demonstrated that both VPS45 and PEP12 are allele-specific high-copy suppressors of pep7-20 mutant phenotypes [6].
  • The class D VPS genes include VPS21, PEP12, and VPS45, which appear to encode components of a membrane fusion complex involved in Golgi-to-endosome transport [7].
  • Mutations in the class D gene VPS45 can be used to define a second transport intermediate along the vacuolar biogenesis pathway, Golgi-derived transport vesicles carrying vacuolar membrane proteins on their way to the vacuole [8].

Anatomical context of VPS45

  • We propose that activated-Vps21p interacts with its effector, Vac1p, which interacts with Vps45p to regulate the Golgi to endosome SNARE complex [9].
  • Vac1 proteins with mutant FYVE fingers still associated with membranes but showed vacuolar protein sorting defects and reduced interactions with Vps45p and activated Vps21p [9].
  • This accumulation of potential transport vesicles indicates that Vps45p may facilitate the targeting and/or fusion of these vesicles in the vacuolar protein sorting pathway [5].
  • Because the entire yeast secretory pathway is functional after the temperature-induced inactivation of Vps45p, we conclude that the accumulated vesicles represent transport intermediates between the Golgi and the vacuole [10].
  • In contrast, SM proteins that mediate Golgi and endoplasmic reticulum fusion (Sly1 and Vps45) bind only to short N-terminal sequences of syntaxins 5, 16, or 18, independently of their H(abc) domains and SNARE motifs [11].

Associations of VPS45 with chemical compounds

  • Several of the encoded proteins, including Pep12p/Vps6p (an endosomal target (t) SNARE) and Vps45p (a Sec1p homologue), bind each other directly [1] [12].

Other interactions of VPS45

  • The functions of Pep12p, Vps45p, and Vps21p indicate that key aspects of Golgi-to-endosome trafficking are similar to other vesicle-mediated transport steps, although the role of Vac1p suggests that there are also novel components of the VPS pathway [13].
  • Using a combination of immunofluorescence localization and pulse/chase immunoprecipitation analysis, we demonstrate that, in addition to ALP, the vacuolar syntaxin Vam3p also follows this VPS45/27-independent pathway to the vacuole [4].
  • The vacuolar ATPase subunit Vph1p transits to the vacuole in the Golgi-derived transport vesicles, as defined by mutations in VPS45, and through the PVC, as defined by mutations in VPS27 [4].
  • Vps33p also interacts with Pep12p, a known interactor of the SM protein Vps45p [14].
  • Thus, the early Vps45-Tlg2p-dependent step of the Cvt pathway appears to be mechanistically distinct from the comparable stage in macroautophagy [15].

Analytical, diagnostic and therapeutic context of VPS45


  1. The Sec1p/Munc18 protein Vps45p binds its cognate SNARE proteins via two distinct modes. Carpp, L.N., Ciufo, L.F., Shanks, S.G., Boyd, A., Bryant, N.J. J. Cell Biol. (2006) [Pubmed]
  2. The Sec1p/Munc18 (SM) protein, Vps45p, cycles on and off membranes during vesicle transport. Bryant, N.J., James, D.E. J. Cell Biol. (2003) [Pubmed]
  3. How Tlg2p/syntaxin 16 'snares' Vps45. Dulubova, I., Yamaguchi, T., Gao, Y., Min, S.W., Huryeva, I., Südhof, T.C., Rizo, J. EMBO J. (2002) [Pubmed]
  4. The membrane protein alkaline phosphatase is delivered to the vacuole by a route that is distinct from the VPS-dependent pathway. Piper, R.C., Bryant, N.J., Stevens, T.H. J. Cell Biol. (1997) [Pubmed]
  5. Mutations in the VPS45 gene, a SEC1 homologue, result in vacuolar protein sorting defects and accumulation of membrane vesicles. Cowles, C.R., Emr, S.D., Horazdovsky, B.F. J. Cell. Sci. (1994) [Pubmed]
  6. Genetic interactions between a pep7 mutation and the PEP12 and VPS45 genes: evidence for a novel SNARE component in transport between the Saccharomyces cerevisiae Golgi complex and endosome. Webb, G.C., Hoedt, M., Poole, L.J., Jones, E.W. Genetics (1997) [Pubmed]
  7. VPS21 controls entry of endocytosed and biosynthetic proteins into the yeast prevacuolar compartment. Gerrard, S.R., Bryant, N.J., Stevens, T.H. Mol. Biol. Cell (2000) [Pubmed]
  8. Traffic into the prevacuolar/endosomal compartment of Saccharomyces cerevisiae: a VPS45-dependent intracellular route and a VPS45-independent, endocytic route. Bryant, N.J., Piper, R.C., Gerrard, S.R., Stevens, T.H. Eur. J. Cell Biol. (1998) [Pubmed]
  9. The phosphatidylinositol 3-phosphate binding protein Vac1p interacts with a Rab GTPase and a Sec1p homologue to facilitate vesicle-mediated vacuolar protein sorting. Tall, G.G., Hama, H., DeWald, D.B., Horazdovsky, B.F. Mol. Biol. Cell (1999) [Pubmed]
  10. Yeast Vps45p is a Sec1p-like protein required for the consumption of vacuole-targeted, post-Golgi transport vesicles. Piper, R.C., Whitters, E.A., Stevens, T.H. Eur. J. Cell Biol. (1994) [Pubmed]
  11. Convergence and divergence in the mechanism of SNARE binding by Sec1/Munc18-like proteins. Dulubova, I., Yamaguchi, T., Arac, D., Li, H., Huryeva, I., Min, S.W., Rizo, J., Sudhof, T.C. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  12. Vac1p coordinates Rab and phosphatidylinositol 3-kinase signaling in Vps45p-dependent vesicle docking/fusion at the endosome. Peterson, M.R., Burd, C.G., Emr, S.D. Curr. Biol. (1999) [Pubmed]
  13. A novel Sec18p/NSF-dependent complex required for Golgi-to-endosome transport in yeast. Burd, C.G., Peterson, M., Cowles, C.R., Emr, S.D. Mol. Biol. Cell (1997) [Pubmed]
  14. The Sec1/Munc18 protein, Vps33p, functions at the endosome and the vacuole of Saccharomyces cerevisiae. Subramanian, S., Woolford, C.A., Jones, E.W. Mol. Biol. Cell (2004) [Pubmed]
  15. Cytoplasm to vacuole trafficking of aminopeptidase I requires a t-SNARE-Sec1p complex composed of Tlg2p and Vps45p. Abeliovich, H., Darsow, T., Emr, S.D. EMBO J. (1999) [Pubmed]
  16. Molecular cloning of a mammalian homologue of the yeast vesicular transport protein vps45. El-Husseini, A.E., Guthrie, H., Snutch, T.P., Vincent, S.R. Biochim. Biophys. Acta (1997) [Pubmed]
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