Defining 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....
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Published in: | The EMBO journal 2022-09, Vol.41 (17), p.e110698-n/a |
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Main Authors: | , , , , , , , , , , |
Format: | Article |
Language: | eng |
Subjects: | |
Online Access: | Get full text |
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Summary: | 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, ARL5A and ARL5B were found to interact with and recruit phosphatidylinositol 4‐kinase beta (PI4KB) at trans‐Golgi, thus promoting PI4KB's function in PI4P synthesis and protein secretion.
Synopsis
The Arf GTPase family is involved in a wide range of cellular regulation events. Here, an unbiased search for its members' effector networks allowed functional investigations into the regulation of phospholipase D1 (PLD1) by ARL11/14, and of phosphatidylinositol 4‐kinase beta (PI4KB) by ARL5A/5B.
miniTurboID combined with mass spectrometry reveals proximal interaction networks for the Arf family of small GTPases.
ARL11/14 bind and activate PLD1.
ARL11/14 act through PLD1 to promote phagocytosis in macrophages.
ARL5A/5B recruit PI4KB to increase PI(4)P synthesis and promote protein secretion.
Proteomic analysis of Arf GTPase family interactors reveals a mechanism through which PI(4)P synthesis is regulated. |
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ISSN: | 0261-4189 1460-2075 |