Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation.


Journal

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

Informations de publication

Date de publication:
10 02 2021
Historique:
received: 16 09 2020
accepted: 06 01 2021
entrez: 11 2 2021
pubmed: 12 2 2021
medline: 19 3 2021
Statut: epublish

Résumé

Caveolae are spherically shaped nanodomains of the plasma membrane, generated by cooperative assembly of caveolin and cavin proteins. Cavins are cytosolic peripheral membrane proteins with negatively charged intrinsically disordered regions that flank positively charged α-helical regions. Here, we show that the three disordered domains of Cavin1 are essential for caveola formation and dynamic trafficking of caveolae. Electrostatic interactions between disordered regions and α-helical regions promote liquid-liquid phase separation behaviour of Cavin1 in vitro, assembly of Cavin1 oligomers in solution, generation of membrane curvature, association with caveolin-1, and Cavin1 recruitment to caveolae in cells. Removal of the first disordered region causes irreversible gel formation in vitro and results in aberrant caveola trafficking through the endosomal system. We propose a model for caveola assembly whereby fuzzy electrostatic interactions between Cavin1 and caveolin-1 proteins, combined with membrane lipid interactions, are required to generate membrane curvature and a metastable caveola coat.

Identifiants

pubmed: 33568658
doi: 10.1038/s41467-021-21035-4
pii: 10.1038/s41467-021-21035-4
pmc: PMC7875971
doi:

Substances chimiques

Caveolin 1 0
Cavin1 protein, mouse 0
Membrane Proteins 0
RNA-Binding Proteins 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

931

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Auteurs

Vikas A Tillu (VA)

Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD, Australia.

James Rae (J)

Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD, Australia.
Centre for Microscopy and Microanalysis, St. Lucia, QLD, Australia.

Ya Gao (Y)

Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD, Australia.

Nicholas Ariotti (N)

Electron Microscope Unit, The University of New South Wales, Kensington, NSW, Australia.
Department of Pathology, School of Medical Sciences, The University of New South Wales Kensington, Kensington, NSW, Australia.

Matthias Floetenmeyer (M)

Centre for Microscopy and Microanalysis, St. Lucia, QLD, Australia.

Oleksiy Kovtun (O)

Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD, Australia.
MRC Laboratory of Molecular Biology, Cambridge, UK.

Kerrie-Ann McMahon (KA)

Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD, Australia.

Natasha Chaudhary (N)

Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD, Australia.
The Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada.

Robert G Parton (RG)

Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD, Australia. r.parton@imb.uq.edu.au.
Centre for Microscopy and Microanalysis, St. Lucia, QLD, Australia. r.parton@imb.uq.edu.au.

Brett M Collins (BM)

Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD, Australia. b.collins@imb.uq.edu.au.

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