Vps9 family protein Muk1 is the second Rab5 guanosine nucleotide exchange factor in budding yeast.
VPS9 domains can act as guanine nucleotide exchange factors (GEFs) against small G proteins of the Rab5 family. Saccharomyces cerevisiae vps9Δ mutants have trafficking defects considerably less severe than multiple deletions of the three cognate Rab5 paralogs (Vps21, Ypt52, and Ypt53). Here, we show that Muk1, which also contains a ... VPS9 domain, acts as a second GEF against Vps21, Ypt52, and Ypt53. Muk1 is partially redundant with Vps9 in vivo, with vps9Δ muk1Δ double mutant cells displaying hypersensitivity to temperature and ionic stress, and profound impairments in endocytic and Golgi-endosome trafficking, including defects in sorting through the multivesicular body (MVB). Cells lacking both Vps9 and Muk1 closely phenocopy double and triple knockout strains lacking Rab5 paralogs. Microscopy and overexpression experiments show that Vps9 and Muk1 have distinct localization determinants. These experiments establish Muk1 as the second Rab5 GEF in budding yeast.
J. Biol. Chem.
Date: Apr. 23, 2013
PubMed ID: 23612966
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