Anoctamin 8 tethers endoplasmic reticulum and plasma membrane for assembly of Ca2+ signaling complexes at the ER/PM compartment

Communication and material transfer between membranes and organelles take place at membrane contact sites (MCSs). MCSs between the ER and PM, the ER/PM junctions, are the sites where the ER Ca2+ sensor STIM1 and the PM Ca2+ influx channel Orai1 cluster. MCSs are formed by tether proteins that bridge...

Teljes leírás

Elmentve itt :
Bibliográfiai részletek
Szerzők: Jha Archana
Chung Woo Young
Vachel Laura
Maléth József
Lake Sarah
Zhang Guofeng
Ahuja Malini
Muallem Shmuel
Dokumentumtípus: Cikk
Megjelent: 2019
Sorozat:EMBO JOURNAL 38 No. 12
doi:10.15252/embj.2018101452

mtmt:30738812
Online Access:http://publicatio.bibl.u-szeged.hu/18599
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520 3 |a Communication and material transfer between membranes and organelles take place at membrane contact sites (MCSs). MCSs between the ER and PM, the ER/PM junctions, are the sites where the ER Ca2+ sensor STIM1 and the PM Ca2+ influx channel Orai1 cluster. MCSs are formed by tether proteins that bridge the opposing membranes, but the identity and role of these tethers in receptor-evoked Ca2+ signaling is not well understood. Here, we identified Anoctamin 8 (ANO8) as a key tether in the formation of the ER/PM junctions that is essential for STIM1-STIM1 interaction and STIM1-Orai1 interaction and channel activation at a ER/PM PI(4,5)P2-rich compartment. Moreover, ANO8 assembles all core Ca2+ signaling proteins: Orai1, PMCA, STIM1, IP3 receptors, and SERCA2 at the ER/PM junctions to mediate a novel form of Orai1 channel inactivation by markedly facilitating SERCA2-mediated Ca2+ influx into the ER. This controls the efficiency of receptor-stimulated Ca2+ signaling, Ca2+ oscillations, and duration of Orai1 activity to prevent Ca2+ toxicity. These findings reveal the central role of MCSs in determining efficiency and fidelity of cell signaling. © 2019 The Authors 
700 0 1 |a Chung Woo Young  |e aut 
700 0 1 |a Vachel Laura  |e aut 
700 0 1 |a Maléth József  |e aut 
700 0 1 |a Lake Sarah  |e aut 
700 0 1 |a Zhang Guofeng  |e aut 
700 0 1 |a Ahuja Malini  |e aut 
700 0 1 |a Muallem Shmuel  |e aut 
856 4 0 |u http://publicatio.bibl.u-szeged.hu/18599/1/30738812_Anoctamin8attheER-PMjunctionsfull.pdf  |z Dokumentum-elérés