Bidirectional regulation of calcium release-activated calcium (CRAC) channel by SARAF.
J Cell Biol
; 220(12)2021 12 06.
Article
em En
| MEDLINE
| ID: mdl-34705029
ABSTRACT
Store-operated calcium entry (SOCE) through the Ca2+ release-activated Ca2+ (CRAC) channel is a central mechanism by which cells generate Ca2+ signals and mediate Ca2+-dependent gene expression. The molecular basis for CRAC channel regulation by the SOCE-associated regulatory factor (SARAF) remained insufficiently understood. Here we found that following ER Ca2+ depletion, SARAF facilitates a conformational change in the ER Ca2+ sensor STIM1 that relieves an activation constraint enforced by the STIM1 inactivation domain (ID; aa 475-483) and promotes initial activation of STIM1, its translocation to ER-plasma membrane junctions, and coupling to Orai1 channels. Following intracellular Ca2+ rise, cooperation between SARAF and the STIM1 ID controls CRAC channel slow Ca2+-dependent inactivation. We further show that in T lymphocytes, SARAF is required for proper T cell receptor evoked transcription. Taking all these data together, we uncover a dual regulatory role for SARAF during both activation and inactivation of CRAC channels and show that SARAF fine-tunes intracellular Ca2+ responses and downstream gene expression in cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Sensoras de Cálcio Intracelular
/
Molécula 1 de Interação Estromal
/
Canais de Cálcio Ativados pela Liberação de Cálcio
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Proteína ORAI1
/
Proteínas de Membrana
Limite:
Humans
Idioma:
En
Revista:
J Cell Biol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Israel