Insulin-activated store-operated Ca²⁺ entry via Orai1 induces podocyte actin remodeling and causes proteinuria.

ABSTRACT: Podocyte, the gatekeeper of the glomerular filtration barrier, is a primary target for growth factor and Ca²⁺ signaling whose perturbation leads to proteinuria. However, the effects of insulin action on store-operated Ca²⁺ entry (SOCE) in podocytes remain unknown. Here, we demonstrated that insulin stimulates SOCE by VAMP2-dependent Orai1 trafficking to the plasma membrane. Insulin-activated SOCE triggers actin remodeling and transepithelial albumin leakage via the Ca²⁺-calcineurin pathway in podocytes. Transgenic Orai1 overexpression in mice causes podocyte fusion and impaired glomerular filtration barrier. Conversely, podocyte-specific Orai1 deletion prevents insulin-stimulated SOCE, synaptopodin depletion, and proteinuria. Podocyte injury and albuminuria

SUBMITTER: Kim JH 

PROVIDER: S-EPMC8586150 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature