title: The intersection of Golgi-ER retrograde and autophagic trafficking.
abstract: For decades, a marvelous amount of work has been performed to identify molecules that regulate distinct stages of membrane transport in the ER-Golgi secretory pathway and autophagy, which are implicated in many human diseases. However, an important missing piece in this puzzle is how the cell dynamically coordinates these crisscrossed trafficking pathways in response to different stimuli. Our recent study has identified UVRAG as a mode-switching protein that coordinates Golgi-ER retrograde and autophagic trafficking. UVRAG recognizes phosphatidylinositol-3-phosphate (PtdIns3P) and locates to the ER, where it couples the ER tethering complex containing RINT1 to govern Golgi-ER retrograde transport. Intriguingly, when autophagy is induced, UVRAG undergoes a "partnering shift" from the ER tethering complex to the BECN1 autophagy complex, resulting in concomitant inhibition of Golgi-ER transport and the activation of ATG9 autophagic trafficking. Therefore, Golgi-ER retrograde and autophagy-related membrane trafficking are functionally interdependent and tightly regulated by UVRAG to ensure spatiotemporal fidelity of protein transport and organelle homeostasis, providing distinguished insights into trafficking-related diseases.
authors.affiliation: Department of Molecular Microbiology and Immunology; University of Southern California; Los Angeles, CA USA.
authors.forename: Shanshan
authors.initials: S
authors.lastname: He
authors.affiliation: Department of Molecular Microbiology and Immunology; University of Southern California; Los Angeles, CA USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: O'Connell
authors.affiliation: Department of Molecular Microbiology and Immunology; University of Southern California; Los Angeles, CA USA.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Molecular Microbiology and Immunology; University of Southern California; Los Angeles, CA USA.
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Molecular Microbiology and Immunology; University of Southern California; Los Angeles, CA USA.
authors.forename: Chengyu
authors.initials: C
authors.lastname: Liang
mesh_terms: D000818:Animals; D001343:Autophagy; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D021381:Protein Transport; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D018129:Phosphatidylinositol Phosphates; D025521:Tumor Suppressor Proteins; C055525:phosphatidylinositol 3-phosphate
keywords: Golgi-ER trafficking; UVRAG; autophagy