A longer isoform of Stim1 is a negative SOCE regulator but increases cAMP-modulated NFAT signaling.

ABSTRACT: Alternative splicing is a potent modifier of protein function. Stromal interaction molecule 1 (Stim1) is the essential activator of store-operated Ca²⁺ entry (SOCE) triggering activation of transcription factors. Here, we characterize Stim1A, a splice variant with an additional 31 amino acid domain inserted in frame within its cytosolic domain. Prominent expression of exon A is found in astrocytes, heart, kidney, and testes. Full-length Stim1A functions as a dominant-negative regulator of SOCE and I_CRAC, facilitating sequence-specific fast calcium-dependent inactivation and destabilizing gating of Orai channels. Downregulation or absence of native Stim1A results in increased SOCE. Despite reducing SOCE, Stim1A leads to increased NFAT translocation. Differential proteo

SUBMITTER: Knapp ML 

PROVIDER: S-EPMC8892257 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature