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bioRxiv · 10.1101/312546

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

Shi, M.·Chen, B.·Boh, B. K.·Zhou, Y.·Divyanshu, M.·Tie, H. C.·Lu, L.
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Abstract

The endosome-to-Golgi or endocytic retrograde trafficking pathway is an important post-Golgi recycling route. We made a novel discovery that the retrograde trafficking of cargos is inhibited and stimulated by the absence and presence, respectively, of amino acids (AAs), especially glutamine. By testing components of the AA-stimulated mTORC1 signaling pathway, we demonstrated 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 functions as a guanine nucleotide exchange factor to activate Arl5, which, together with GARP, a tethering factor, probably facilitates the endosome-to-Golgi trafficking.

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Shi, M., Chen, B., Boh, B. K., Zhou, Y., Divyanshu, M., Tie, H. C., Lu, L.. 2018-05-01. Amino acids stimulate the endosome-to-Golgi trafficking through Ragulator and small GTPase Arl5. https://doi.org/10.1101/312546

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