RT Journal Article SR Electronic T1 Amino acids stimulate the endosome-to-Golgi trafficking through Ragulator and small GTPase Arl5 JF bioRxiv FD Cold Spring Harbor Laboratory SP 312546 DO 10.1101/312546 A1 Meng Shi A1 Bing Chen A1 Boon Kim Boh A1 Yan Zhou A1 Divyanshu Mahajan A1 Hieng Chiong Tie A1 Lei Lu YR 2018 UL http://biorxiv.org/content/early/2018/05/01/312546.abstract AB 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.