GLIPR2 is a negative regulator of autophagy and the BECN1-ATG14-containing phosphatidylinositol 3-kinase complex.


Journal

Autophagy
ISSN: 1554-8635
Titre abrégé: Autophagy
Pays: United States
ID NLM: 101265188

Informations de publication

Date de publication:
10 2021
Historique:
pubmed: 24 11 2020
medline: 8 4 2022
entrez: 23 11 2020
Statut: ppublish

Résumé

A key mediator of macroautophagy/autophagy induction is the class III phosphatidylinositol 3-kinase complex I (PtdIns3K-C1) consisting of PIK3C3/VPS34, PIK3R4/VPS15, BECN1, and ATG14. Although several proteins are known to enhance or decrease PtdIns3K-C1 activity, our understanding of the molecular regulation of PtdIns3K-C1 is still incomplete. Previously, we identified a Golgi-associated protein, GLIPR2, in a screen for proteins that interact with amino acids 267-284 of BECN1, a region of BECN1 sufficient to induce autophagy when fused to a cell penetrating leader sequence. In this study, we used CRISPR-Cas9-mediated depletion of GLIPR2 in cells and mice to investigate the role of GLIPR2 in the regulation of autophagy and PtdIns3K-C1 activity. Depletion of GLIPR2 in HeLa cells increased autelophagic flux and generation of phosphatidylinositol 3-phosphate (PtdIns3P).

Identifiants

pubmed: 33222586
doi: 10.1080/15548627.2020.1847798
pmc: PMC8526008
doi:

Substances chimiques

ATG14 protein, human 0
Adaptor Proteins, Vesicular Transport 0
Autophagy-Related Proteins 0
BECN1 protein, human 0
Beclin-1 0
Becn1 protein, mouse 0
GLIPR2 protein, human 0
Membrane Proteins 0
Class III Phosphatidylinositol 3-Kinases EC 2.7.1.137

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

2891-2904

Subventions

Organisme : NIGMS NIH HHS
ID : R15 GM122035
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI109725
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI142784
Pays : United States

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Auteurs

Yuting Zhao (Y)

Center for Autophagy Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Zhongju Zou (Z)

Center for Autophagy Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Daxiao Sun (D)

The State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.

Yue Li (Y)

Department of Chemistry and Biochemistry, North Dakota State University, Fargo, ND, USA.

Sangita C Sinha (SC)

Department of Chemistry and Biochemistry, North Dakota State University, Fargo, ND, USA.

Li Yu (L)

The State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.

Lynda Bennett (L)

Center for Autophagy Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Beth Levine (B)

Center for Autophagy Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

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