The spectrin cytoskeleton integrates endothelial mechanoresponses View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2022-07-11

AUTHORS

Sivakami Mylvaganam, Jonathan Plumb, Bushra Yusuf, Ren Li, Chien-Yi Lu, Lisa A. Robinson, Spencer A. Freeman, Sergio Grinstein

ABSTRACT

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. More... »

PAGES

1226-1238

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41556-022-00953-5

DOI

http://dx.doi.org/10.1038/s41556-022-00953-5

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1149372559

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/35817960


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