Avl9 defines a family of GTPase-activating proteins that regulate diverse cell biological functions
Vignogna, R. C.; Fromme, J. C.
Show abstract
Ras-related GTPases are molecular switches regulating hundreds of signaling and trafficking pathways in cells. Many GTPase regulators remain to be identified despite extensive genetic and biochemical screens. Here we present the results of computational protein-protein interaction screens and functional experiments identifying the DENN domain protein Avl9 as a GTPase-activating protein for Arf1. Avl9 is involved in secretion and cell migration, but its molecular function has not been characterized. We determined that Avl9 possesses robust Arf-GAP activity and is recruited to secretory vesicles by Rab8. We find that Avl9 function is conserved in humans and enhances cell migration. We propose that several other DENN domain proteins are also candidate GAPs, and we demonstrate that one candidate previously characterized as a Rab-GEF, DENND6A, exhibits strong Arf-GAP activity towards ARL8B, explaining its role in lysosome positioning. Collectively, this work uncovers a family of monomeric DENN GAP proteins that regulate diverse cell biological pathways.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Src activates retrograde membrane traffic through phosphorylation of GBF1 97%
- The KASH5 protein involved in meiotic chromosomal movements is a novel dynein activating adaptor 96%
- C-terminal tagging, transmembrane domain hydrophobicity, and an ER retention motif influence the secretory trafficking of the inner nuclear membrane protein emerin 96%
Similar papers in this journal
- Rab2 and Arl8/BORC control retrograde axonal transport of dense core vesicles via Syd/dJIP3/4 and RUFY dynein adaptors 97%
- The ER cholesterol sensor SCAP promotes CARTS biogenesis at ER-Golgi contact sites 96%
- A RAB7A Phosphoswitch Coordinates Rubicon Homology Protein Regulation of PINK1/Parkin-Dependent Mitophagy 95%
Similar papers in this journal
- Structural basis for autophagy inhibition by the human Rubicon-Rab7 complex 96%
- Structure and mechanism of the human CTDNEP1-NEP1R1 membrane protein phosphatase complex necessary to maintain ER membrane morphology 96%
- A noncanonical GTPase signaling mechanism controls exit from mitosis in budding yeast 96%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.