Your browser doesn't support javascript.
loading
PIP2 and septin control STIM1/Orai1 assembly by regulating cytoskeletal remodeling via a CDC42-WASP/WAVE-ARP2/3 protein complex.
de Souza, Lorena Brito; Ong, Hwei Ling; Liu, Xibao; Ambudkar, Indu S.
Afiliación
  • de Souza LB; Secretory Physiology Section, NIDCR, NIH, Bldg. 10/Room 1N-113, Bethesda, MD 20892, USA.
  • Ong HL; Secretory Physiology Section, NIDCR, NIH, Bldg. 10/Room 1N-113, Bethesda, MD 20892, USA. Electronic address: ongh@mail.nih.gov.
  • Liu X; Secretory Physiology Section, NIDCR, NIH, Bldg. 10/Room 1N-113, Bethesda, MD 20892, USA.
  • Ambudkar IS; Secretory Physiology Section, NIDCR, NIH, Bldg. 10/Room 1N-113, Bethesda, MD 20892, USA. Electronic address: indu.ambudkar@nih.gov.
Cell Calcium ; 99: 102475, 2021 11.
Article en En | MEDLINE | ID: mdl-34601312
Store-operated calcium entry (SOCE) is triggered by assembly of Orai1 with STIM proteins in ER-PM junctions. Plasma membrane PIP2 as well as PIP2-binding protein, SEPT4, significantly impact Orai1-STIM1 interaction. While septins and PIP2 can organize the actin cytoskeleton, it is unclear whether the status of actin within the junctions contributes to SOCE. We report herein that actin remodeling modulates STIM1 clustering. Our findings show that a PIP2- and SEPT4-dependent mechanism involving CDC42, WASP/WAVE, and ARP2 regulates actin remodeling into a ring-like structure around STIM1 puncta. CDC42 localization in the ER-plasma membrane region is enhanced following ER-Ca2+ store depletion. PIP2 depletion or knockdown of SEPT4 attenuate the recruitment of CDC42 to the ER-PM region. Importantly, knockdown of SEPT4, or CDC42+ARP2, disrupts the organization of actin as well as STIM1 clustering. Consequently, Orai1 recruitment to STIM1 puncta, SOCE, and NFAT translocation to the nucleus are all attenuated. Ca2+ influx induced by STIM1-C terminus is not affected by CDC42 knockdown. In aggregate, our findings reveal that PIP2 and SEPT4 affect Orai1/STIM1 clustering by coordinating actin remodeling within ER-PM junctions. This dynamic reorganization of actin has an important role in regulation of SOCE and downstream Ca2+-dependent effector functions.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Complejo 2-3 Proteico Relacionado con la Actina / Septinas Idioma: En Revista: Cell Calcium Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Complejo 2-3 Proteico Relacionado con la Actina / Septinas Idioma: En Revista: Cell Calcium Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos