Premium
Cytoplasmic control of Rab family small GTP ases through BAG 6
Author(s) -
Takahashi Toshiki,
Minami Setsuya,
Tsuchiya Yugo,
Tajima Kazu,
Sakai Natsumi,
Suga Kei,
Hisanaga Shinichi,
Ohbayashi Norihiko,
Fukuda Mitsunori,
Kawahara Hiroyuki
Publication year - 2019
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201846794
Subject(s) - rab , gtp' , cytoplasm , chemistry , microbiology and biotechnology , biology , biochemistry , gtpase , enzyme
Rab family small GTP ases are master regulators of distinct steps of intracellular vesicle trafficking in eukaryotic cells. GDP ‐bound cytoplasmic forms of Rab proteins are prone to aggregation due to the exposure of hydrophobic groups but the machinery that determines the fate of Rab species in the cytosol has not been elucidated in detail. In this study, we find that BAG 6 ( BAT 3/Scythe) predominantly recognizes a cryptic portion of GDP ‐associated Rab8a, while its major GTP ‐bound active form is not recognized. The hydrophobic residues of the Switch I region of Rab8a are essential for its interaction with BAG 6 and the degradation of GDP ‐Rab8a via the ubiquitin‐proteasome system. BAG 6 prevents the excess accumulation of inactive Rab8a, whose accumulation impairs intracellular membrane trafficking. BAG 6 binds not only Rab8a but also a functionally distinct set of Rab family proteins, and is also required for the correct distribution of Golgi and endosomal markers. From these observations, we suggest that Rab proteins represent a novel set of substrates for BAG 6, and the BAG 6‐mediated pathway is associated with the regulation of membrane vesicle trafficking events in mammalian cells.