The spectrin cytoskeleton integrates endothelial mechanoresponses.
Journal
Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
14
09
2021
accepted:
01
06
2022
pubmed:
12
7
2022
medline:
11
8
2022
entrez:
11
7
2022
Statut:
ppublish
Résumé
Physiological blood flow induces the secretion of vasoactive compounds, notably nitric oxide, and promotes endothelial cell elongation and reorientation parallel to the direction of applied shear. How shear is sensed and relayed to intracellular effectors is incompletely understood. Here, we demonstrate that an apical spectrin network is essential to convey the force imposed by shear to endothelial mechanosensors. By anchoring CD44, spectrins modulate the cell surface density of hyaluronan and sense and translate shear into changes in plasma membrane tension. Spectrins also regulate the stability of apical caveolae, where the mechanosensitive PIEZO1 channels are thought to reside. Accordingly, shear-induced PIEZO1 activation and the associated calcium influx were absent in spectrin-deficient cells. As a result, cell realignment and flow-induced endothelial nitric oxide synthase stimulation were similarly dependent on spectrin. We conclude that the apical spectrin network is not only required for shear sensing but also transmits and distributes the resulting tensile forces to mechanosensors that elicit protective and vasoactive responses.
Identifiants
pubmed: 35817960
doi: 10.1038/s41556-022-00953-5
pii: 10.1038/s41556-022-00953-5
doi:
Substances chimiques
Spectrin
12634-43-4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1226-1238Subventions
Organisme : CIHR
ID : PJT-169180
Pays : Canada
Organisme : CIHR
ID : FDN-143202
Pays : Canada
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
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