A conformational switch in clathrin light chain regulates lattice structure and endocytosis at the plasma membrane of mammalian cells.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
09 02 2023
Historique:
received: 05 05 2022
accepted: 25 01 2023
entrez: 9 2 2023
pubmed: 10 2 2023
medline: 14 2 2023
Statut: epublish

Résumé

Conformational changes in endocytic proteins are regulators of clathrin-mediated endocytosis. Three clathrin heavy chains associated with clathrin light chains (CLC) assemble into triskelia that link into a geometric lattice that curves to drive endocytosis. Structural changes in CLC have been shown to regulate triskelia assembly in solution, yet the nature of these changes, and their effects on lattice growth, curvature, and endocytosis in cells are unknown. Here, we develop a new correlative fluorescence resonance energy transfer (FRET) and platinum replica electron microscopy method, named FRET-CLEM. With FRET-CLEM, we measure conformational changes in clathrin at thousands of individual morphologically distinct clathrin-coated structures. We discover that the N-terminus of CLC repositions away from the plasma membrane and triskelia vertex as coats curve. Preventing this conformational switch with chemical tools increases lattice sizes and inhibits endocytosis. Thus, a specific conformational switch in the light chain regulates lattice curvature and endocytosis in mammalian cells.

Identifiants

pubmed: 36759616
doi: 10.1038/s41467-023-36304-7
pii: 10.1038/s41467-023-36304-7
pmc: PMC9911608
doi:

Substances chimiques

Clathrin Light Chains 0
Clathrin 0
Clathrin Heavy Chains 114899-12-6

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

732

Informations de copyright

© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

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Auteurs

Kazuki Obashi (K)

Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, 50 South Drive, Building 50, Bethesda, MD, 20892, USA.

Kem A Sochacki (KA)

Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, 50 South Drive, Building 50, Bethesda, MD, 20892, USA.

Marie-Paule Strub (MP)

Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, 50 South Drive, Building 50, Bethesda, MD, 20892, USA.

Justin W Taraska (JW)

Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, 50 South Drive, Building 50, Bethesda, MD, 20892, USA. justin.taraska@nih.gov.

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