Mso1 is a novel component of the yeast exocytic SNARE complex.
The yeast exocytic SNARE complex consists of one molecule each of the Sso1/2 target SNAREs, Snc1/2 vesicular SNAREs, and the Sec9 target SNARE, which form a fusion complex that is conserved in evolution. Another protein, Sec1, binds to the SNARE complex to facilitate assembly. We show that Mso1, a Sec1-interacting protein, also binds to the SNARE complex and plays a role in mediating Sec1 functions. Like Sec1, Mso1 bound to SNAREs in cells containing SNARE complexes (i.e. wild-type, sec1-1, and sec18-1 cells), but not in cells in which complex formation is inhibited (i.e. sec4-8 cells). Nevertheless, Mso1 remained associated with Sec1 even in sec4-8 cells, indicating that they act as a pair. Mso1 localized primarily to the plasma membrane of the bud when SNARE complex formation was not impaired but was mostly in the cytoplasm when assembly was prevented. Genetic studies suggest that Mso1 enhances Sec1 function while attenuating Sec4 GTPase function. This dual action may impart temporal regulation between Sec4 turnoff and Sec1-mediated SNARE assembly. Notably, a small region at the C terminus of Mso1 is conserved in the mammalian Munc13/Mint proteins and is necessary for proper membrane localization. Overexpression of Mso1 lacking this domain (Mso1-(1-193)) inhibited the growth of cells bearing an attenuated Sec4 GTPase. These results suggest that Mso1 is a component of the exocytic SNARE complex and a possible ortholog of the Munc13/Mint proteins.
Castillo-Flores
Antonio
A
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Weinberger
Adina
A
Robinson
Micah
M
Gerst
Jeffrey E
JE
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000737:chemistry; D049109:Cell Proliferation; D006801:Humans; D007700:Kinetics; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics; D050600:SNARE Proteins / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000502:physiology*; D017385:Sequence Homology; D020691:rab GTP-Binding Proteins / Q000502:physiology
C079091:APBA1 protein, human; D048868:Adaptor Proteins, Signal Transducing; C106953:MSO1 protein, S cerevisiae; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050600:SNARE Proteins; D029701:Saccharomyces cerevisiae Proteins; C485548:UNC13B protein, human; C064320:SEC4 protein, S cerevisiae; D020691:rab GTP-Binding Proteins