CHC22 clathrin recruitment to the early secretory pathway requires two-site interaction with SNX5 and p115.

CHC22 Clathrin Golgi bypass Sorting nexin 5 p115

Journal

The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664

Informations de publication

Date de publication:
19 Aug 2024
Historique:
received: 04 10 2023
accepted: 17 07 2024
revised: 15 07 2024
medline: 20 8 2024
pubmed: 20 8 2024
entrez: 19 8 2024
Statut: aheadofprint

Résumé

The two clathrin isoforms, CHC17 and CHC22, mediate separate intracellular transport routes. CHC17 performs endocytosis and housekeeping membrane traffic in all cells. CHC22, expressed most highly in skeletal muscle, shuttles the glucose transporter GLUT4 from the ERGIC (endoplasmic-reticulum-to-Golgi intermediate compartment) directly to an intracellular GLUT4 storage compartment (GSC), from where GLUT4 can be mobilized to the plasma membrane by insulin. Here, molecular determinants distinguishing CHC22 from CHC17 trafficking are defined. We show that the C-terminal trimerization domain of CHC22 interacts with SNX5, which also binds the ERGIC tether p115. SNX5, and the functionally redundant SNX6, are required for CHC22 localization independently of their participation in the endosomal ESCPE-1 complex. In tandem, an isoform-specific patch in the CHC22 N-terminal domain separately mediates binding to p115. This dual mode of clathrin recruitment, involving interactions at both N- and C-termini of the heavy chain, is required for CHC22 targeting to ERGIC membranes to mediate the Golgi-bypass route for GLUT4 trafficking. Interference with either interaction inhibits GLUT4 targeting to the GSC, defining a bipartite mechanism regulating a key pathway in human glucose metabolism.

Identifiants

pubmed: 39160272
doi: 10.1038/s44318-024-00198-y
pii: 10.1038/s44318-024-00198-y
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Wellcome Trust (WT)
ID : 107858/Z/15/Z
Organisme : Wellcome Trust (WT)
ID : 219856/Z/19/Z
Organisme : Wellcome Trust (WT)
ID : 104568/Z/14/Z
Organisme : Wellcome Trust (WT)
ID : 220260/Z/20/Z
Organisme : UKRI | MRC | Medical Research Foundation
ID : MR/S008144/1
Organisme : UKRI | Biotechnology and Biological Sciences Research Council (BBSRC)
ID : BB/V001221/1
Organisme : UKRI | Medical Research Council (MRC)
ID : MR/L007363/1
Organisme : UKRI | Medical Research Council (MRC)
ID : MR/P018807/1
Organisme : Royal Society (The Royal Society)
ID : RSRP/R1/211004

Informations de copyright

© 2024. The Author(s).

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Auteurs

Joshua Greig (J)

Structural and Molecular Biology, Division of Biosciences, University College London, London, WC1E 6BT, UK.
Institute of Structural and Molecular Biology, Birkbeck and University College London, London, WC1E 7HX, UK.

George T Bates (GT)

Structural and Molecular Biology, Division of Biosciences, University College London, London, WC1E 6BT, UK.
Institute of Structural and Molecular Biology, Birkbeck and University College London, London, WC1E 7HX, UK.

Daowen I Yin (DI)

Structural and Molecular Biology, Division of Biosciences, University College London, London, WC1E 6BT, UK.
Institute of Structural and Molecular Biology, Birkbeck and University College London, London, WC1E 7HX, UK.

Kit Briant (K)

Structural and Molecular Biology, Division of Biosciences, University College London, London, WC1E 6BT, UK.
Institute of Structural and Molecular Biology, Birkbeck and University College London, London, WC1E 7HX, UK.

Boris Simonetti (B)

School of Biochemistry, Faculty of Life Sciences, University of Bristol, Bristol, UK.

Peter J Cullen (PJ)

School of Biochemistry, Faculty of Life Sciences, University of Bristol, Bristol, UK.

Frances M Brodsky (FM)

Structural and Molecular Biology, Division of Biosciences, University College London, London, WC1E 6BT, UK. f.brodsky@ucl.ac.uk.
Institute of Structural and Molecular Biology, Birkbeck and University College London, London, WC1E 7HX, UK. f.brodsky@ucl.ac.uk.

Classifications MeSH