2. Academic Validation
  3. PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and Atg9 transport by differential interactions with the ER tether and the beclin 1 complex

PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and Atg9 transport by differential interactions with the ER tether and the beclin 1 complex

  • Nat Cell Biol. 2013 Oct;15(10):1206-1219. doi: 10.1038/ncb2848.
Shanshan He # 1,  Duojiao Ni # 1,  Binyun Ma # 1,  Joo-Hyung Lee 1,  Tian Zhang 1,  Irene Ghozalli 1,  Sara Dolatshahi Pirooz 1,  Zhen Zhao 1,  Nagakumar Bharatham 2,  Baihong Li 2,  Soohwan Oh 1,  Wen-Hwa Lee 3,  Yoshinori Takahashi 4,  Hong-Gang Wang 4,  Arlet Minassian 1,  Pinghui Feng 1,  Vojo Deretic 5,  Rainer Pepperkok 6,  Mitsuo Tagaya 7,  Ho Sup Yoon 2 8,  Chengyu Liang 1
Affiliations

Affiliations

  • 1 Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA 90033, USA.
  • 2 Division of Structural Biology and Biochemistry, School of Biological Sciences, Nanyang Technological University, Singapore 637551.
  • 3 Department of Biological Chemistry, University of California, Irvine, Irvine, California 92697.
  • 4 Department of Pharmacology and Penn State Hershey Cancer Institute; The Pennsylvania State University College of Medicine; Hershey, PA USA.
  • 5 Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131.
  • 6 European Molecular Biology Laboratory, Heidelberg, Cell Biology/Cell Biophysics Unit, Meyerhofstr. 1, D-69117 Heidelberg Germany.
  • 7 School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0393, Japan.
  • 8 Department of Genetic Engineering, College of Life Sciences, Kyung Hee University, Yongin-si, Gyeonggi-do, 446-701, Republic of Korea.
  • # Contributed equally.
PMID: 24056303 DOI: 10.1038/ncb2848
Abstract

Endoplasmic reticulum (ER)-Golgi membrane transport and Autophagy are intersecting trafficking pathways that are tightly regulated and crucial for homeostasis, development and disease. Here, we identify UVRAG, a beclin-1-binding autophagic factor, as a phosphatidylinositol-3-phosphate (PtdIns(3)P)-binding protein that depends on PtdIns(3)P for its ER localization. We further show that UVRAG interacts with RINT-1, and acts as an integral component of the RINT-1-containing ER tethering complex, which couples phosphoinositide metabolism to COPI-vesicle tethering. Displacement or knockdown of UVRAG profoundly disrupted COPI cargo transfer to the ER and Golgi integrity. Intriguingly, Autophagy caused the dissociation of UVRAG from the ER tether, which in turn worked in concert with the Bif-1-beclin-1-PI(3)KC3 complex to mobilize Atg9 translocation for autophagosome formation. These findings identify a regulatory mechanism that coordinates Golgi-ER retrograde and autophagy-related vesicular trafficking events through physical and functional interactions between UVRAG, phosphoinositide and their regulatory factors, thereby ensuring spatiotemporal fidelity of membrane trafficking and maintenance of organelle homeostasis.

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