Open AccessFatty-acid binding protein 5 modulates the SAR1 GTPase cycle and enhances budding of large COPII cargoes
Author(s) -
David B. Melville,
Amita Gorur,
Randy Schekman
Publication year - 2019
Publication title -
molecular biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.463
H-Index - 225
eISSN - 1939-4586
pISSN - 1059-1524
DOI - 10.1091/mbc.e18-09-0548
Subject(s) - copii , gtpase , microbiology and biotechnology , biology , copi , budding , small gtpase , vesicular transport proteins , gtpase activating protein , golgi apparatus , transport protein , secretory pathway , g protein , endoplasmic reticulum , signal transduction , endosome , vacuolar protein sorting , intracellular
COPII-coated vesicles are the primary mediators of ER-to-Golgi trafficking. Sar1, one of the five core COPII components, is a highly conserved small GTPase, which, upon GTP binding, recruits the other COPII proteins to the ER membrane. It has been hypothesized that the changes in the kinetics of SAR1 GTPase may allow for the secretion of large cargoes. Here we developed a cell-free assay to recapitulate COPII-dependent budding of large lipoprotein cargoes from the ER. We identified fatty-acid binding protein 5 (FABP5) as an enhancer of this budding process. We found that FABP5 promotes the budding of particles ∼150 nm in diameter and modulates the kinetics of the SAR1 GTPase cycle. We further found that FABP5 enhances the trafficking of lipoproteins and of other cargoes, including collagen. These data identify a novel regulator of SAR1 GTPase activity and highlight the importance of this activity for trafficking of large cargoes.