biostudies-literatureLi FLNCI NIH HHSNational Institutes of HealthNIGMS NIH HHSNIH HHSe110698https://www.ebi.ac.uk/biostudies/studies/S-EPMC9433938biostudies-literatureUnknown41(17)The Arf GTPase family is involved in a wide range of cellular regulation including membrane trafficking and organelle-structure assembly. Here, we have generated a proximity interaction network for the Arf family using the miniTurboID approach combined with TMT-based quantitative mass spectrometry. Our interactome confirmed known interactions and identified many novel interactors that provide leads for defining Arf pathway cell biological functions. We explored the unexpected finding that phospholipase D1 (PLD1) preferentially interacts with two closely related but poorly studied Arf family GTPases, ARL11 and ARL14, showing that PLD1 is activated by ARL11/14 and may recruit these GTPases to membrane vesicles, and that PLD1 and ARL11 collaborate to promote macrophage phagocytosis. Moreover,The EMBO journalDefining the proximal interaction networks of Arf GTPases reveals a mechanism for the regulation of PLD1 and PI4KB.PMC9433938R01 CA217642GM51586S10 OD023498OD023498R01 GM116897T32 CA009523CA268179R01 CA268179CA217642R01 GM051586GM116897T32CA009523Wu ZGao YQHu CSuhandynata RTAirola MVLi FLBowling FZFranklin JMGuan KLFrohman MAZhou HfalseDefining the proximal interaction networks of Arf GTPases reveals a mechanism for the regulation of PLD1 and PI4KB.The Arf GTPase family is involved in a wide range of cellular regulation including membrane trafficking and organelle-structure assembly. Here, we have generated a proximity interaction network for the Arf family using the miniTurboID approach combined with TMT-based quantitative mass spectrometry. Our interactome confirmed known interactions and identified many novel interactors that provide leads for defining Arf pathway cell biological functions. We explored the unexpected finding that phospholipase D1 (PLD1) preferentially interacts with two closely related but poorly studied Arf family GTPases, ARL11 and ARL14, showing that PLD1 is activated by ARL11/14 and may recruit these GTPases to membrane vesicles, and that PLD1 and ARL11 collaborate to promote macrophage phagocytosis. Moreover,2022-01-01T00:00:00Z2022 Sep2025-04-04T20:07:48.365Z2025-04-04T20:07:48.365ZS-EPMC94339383584413510.15252/embj.2022110698