Yeast homologues of tomosyn and lethal giant larvae function in exocytosis and are associated with the plasma membrane SNARE, Sec9.
We have identified a pair of related yeast proteins, Sro7p and Sro77p, based on their ability to bind to the plasma membrane SNARE (SNARE) protein, Sec9p. These proteins show significant similarity to the Drosophila tumor suppressor, lethal giant larvae and to the neuronal syntaxin-binding protein, tomosyn. SRO7 and SRO77 have redundant functions as loss of both gene products leads to a severe cold-sensitive growth defect that correlates with a severe defect in exocytosis. We show that similar to Sec9, Sro7/77 functions in the docking and fusion of post-Golgi vesicles with the plasma membrane. In contrast to a previous report, we see no defect in actin polarity under conditions where we see a dramatic effect on secretion. This demonstrates that the primary function of Sro7/77, and likely all members of the lethal giant larvae family, is in exocytosis rather than in regulating the actin cytoskeleton. Analysis of the association of Sro7p and Sec9p demonstrates that Sro7p directly interacts with Sec9p both in the cytosol and in the plasma membrane and can associate with Sec9p in the context of a SNAP receptor complex. Genetic analysis suggests that Sro7 and Sec9 function together in a pathway downstream of the Rho3 GTPase. Taken together, our studies suggest that members of the lethal giant larvae/tomosyn/Sro7 family play an important role in polarized exocytosis by regulating SNARE function on the plasma membrane.
Department of Cell Biology, Weill Medical College of Cornell University, New York, New York 10021, USA.
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Lehman
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Rossi
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Adamo
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Brennwald
D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D001692:Biological Transport; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism*; D016764:Cell Polarity; D003080:Cold Temperature; D029721:Drosophila Proteins; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005089:Exocytosis; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000502:physiology; D006026:Glycoside Hydrolases / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics; D008565:Membrane Proteins; D009154:Mutation; D009479:Neuropeptides / Q000737:chemistry / Q000235:genetics; D011233:Precipitin Tests; D050767:Qc-SNARE Proteins; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D025521:Tumor Suppressor Proteins; D043324:beta-Fructofuranosidase; D020741:rho GTP-Binding Proteins
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D029721:Drosophila Proteins; D005656:Fungal Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; D009479:Neuropeptides; D050767:Qc-SNARE Proteins; D011993:Recombinant Fusion Proteins; C090117:SEC9 protein, S cerevisiae; C116430:SRO7 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D025521:Tumor Suppressor Proteins; C081435:l(2)gl protein, Drosophila; D006026:Glycoside Hydrolases; D043324:beta-Fructofuranosidase; D020558:GTP Phosphohydrolases; C074647:RHO3 protein, S cerevisiae; D020741:rho GTP-Binding Proteins