Amino acids stimulate the endosome-to-Golgi trafficking through Ragulator and small GTPase Arl5

Meng Shi, Bing Chen, Divyanshu Mahajan, Boon Kim Boh, Yan Zhou, Bamaprasad Dutta, Hieng Chiong Tie, Siu Kwan Sze, Geng Wu and Lei Lu ()
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Meng Shi: Nanyang Technological University
Bing Chen: Nanyang Technological University
Divyanshu Mahajan: Nanyang Technological University
Boon Kim Boh: Nanyang Technological University
Yan Zhou: Nanyang Technological University
Bamaprasad Dutta: Nanyang Technological University
Hieng Chiong Tie: Nanyang Technological University
Siu Kwan Sze: Nanyang Technological University
Geng Wu: Shanghai Jiao Tong University
Lei Lu: Nanyang Technological University

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: Abstract The endosome-to-Golgi or endocytic retrograde trafficking pathway is an important post-Golgi recycling route. Here we show that amino acids (AAs) can stimulate the retrograde trafficking and regulate the cell surface localization of certain Golgi membrane proteins. By testing components of the AA-stimulated mTORC1 signaling pathway, we demonstrate that SLC38A9, v-ATPase and Ragulator, but not Rag GTPases and mTORC1, are essential for the AA-stimulated trafficking. Arl5, an ARF-like family small GTPase, interacts with Ragulator in an AA-regulated manner and both Arl5 and its effector, the Golgi-associated retrograde protein complex (GARP), are required for the AA-stimulated trafficking. We have therefore identified a mechanistic connection between the nutrient signaling and the retrograde trafficking pathway, whereby SLC38A9 and v-ATPase sense AA-sufficiency and Ragulator might function as a guanine nucleotide exchange factor to activate Arl5, which, together with GARP, a tethering factor, probably facilitates the endosome-to-Golgi trafficking.

Date: 2018
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DOI: 10.1038/s41467-018-07444-y

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