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Yeast Rab5 signaling in endolysosomal trafficking and MVB biogenesis
Author(s) -
Merz Alexey J.,
Paulsel Andrew L.,
Russell Matthew R.G.,
Nickerson Daniel P.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.556.5
Subject(s) - rab , endosome , biogenesis , microbiology and biotechnology , biology , golgi apparatus , activator (genetics) , saccharomyces cerevisiae , guanine nucleotide exchange factor , yeast , signal transduction , gene , gtpase , biochemistry , endoplasmic reticulum , intracellular
Small G proteins of the Rab5 family control traffic through early compartments of the endolysosomal system. Saccharomyces cerevisiae, like mammals, contains three Rab5 paralogs: Vps21, Ypt52, and Ypt53. We present experimental analyses of the roles of the overlapping and distinct functions of these Rabs, and we analyze the proteins that activate and terminate their signaling activities. We demonstrate that Rab5 signaling is essential for the biogenesis of morphologically normal endosomal multivesicular bodies (MVBs) and for the correct targeting of MVB cargos en route from the Golgi or plasma membrane. In addition to the known nucleotide exchange factor Vps9, we identify Muk1 as a second partially redundant activator of Rab5 family members, and we present biochemical and functional studies of the relative contributions of Vps9 and Muk1. As with the Rab5 paralogs themselves, Vps9 and Muk1 are essential for correct sorting of cargo into MVB intraluminal vesicles. Finally, we demonstrate that signaling by Vps21, the most biologically important of the three yeast Rab5 family members, is selectively terminated by the Gyp3 Rab GAP.