STIM2 Induces Activated Conformation of STIM1 to Control Orai1 Function in ER-PM Junctions.
Cell Rep
; 23(2): 522-534, 2018 Apr 10.
Article
en En
| MEDLINE
| ID: mdl-29642009
ABSTRACT
Ca2+ entry mediated by the calcium channel, Orai1, provides critical Ca2+ signals that regulate cell function. The ER-Ca2+ sensor protein, STIM1, recruits and strongly activates Orai1 within ER-PM junctions. STIM2 is a poor activator of Orai1, and its physiological role is not well understood. Herein, we report a crucial function for STIM2 in inducing the activated conformation of STIM1. By using conformational sensors of STIM2 and STIM1, together with protein interaction and functional studies, we show that STIM2 is constitutively localized within ER-PM junctions in ER-Ca2+ store replete cells. Importantly, STIM2 traps STIM1 and triggers remodeling of STIM1 C terminus, causing STIM1/Orai1 coupling and enhancement of Orai1 function in cells with relatively high ER-[Ca2+]. The increase in Ca2+ entry controls Ca2+-dependent transcription factor, NFAT, activation at low [agonist]. Our findings reveal that STIM2 modulates STIM1/Orai1 function to tune the fidelity of receptor-evoked Ca2+ signaling and the physiological response of cells.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Membrana Celular
/
Retículo Endoplásmico
/
Molécula de Interacción Estromal 1
/
Molécula de Interacción Estromal 2
/
Proteína ORAI1
/
Proteínas de Neoplasias
Límite:
Humans
Idioma:
En
Revista:
Cell Rep
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos