Ca2+ signals initiate at immobile IP3 receptors adjacent to ER-plasma membrane junctions. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Thillaiappan, Nagendra; Chavda, Alap; Tovey, Stephen; Prole, David; Taylor, Colin
• Is Part Of: Nature communications. Volume 8:Issue 1(2017)
• Page Start: 1
• Page End: 16
• Publication Date: 2017-12
• Subjects: Biology -- Periodicals; Physical sciences -- Periodicals; 505
• DOI: 10.1038/s41467-017-01644-8
• Languages: English
• ISSNs: 2041-1723

Abstract

Abstract IP3 receptors (IP3 Rs) release Ca2+ from the ER when they bind IP3 and Ca2+ . The spatial organization of IP3 Rs determines both the propagation of Ca2+ signals between IP3 Rs and the selective regulation of cellular responses. Here we use gene editing to fluorescently tag endogenous IP3 Rs, and super-resolution microscopy to determine the geography of IP3 Rs and Ca2+ signals within living cells. We show that native IP3 Rs cluster within ER membranes. Most IP3 R clusters are mobile, moved by diffusion and microtubule motors. Ca2+ signals are generated by a small population of immobile IP3 Rs. These IP3 Rs are licensed to respond, but they do not readily mix with mobile IP3 Rs. The licensed IP3 Rs reside alongside ER-plasma membrane junctions where STIM1, which regulates store-operated Ca2+ entry, accumulates after depletion of Ca2+ stores. IP3 Rs tethered close to ER-plasma membrane junctions are licensed to respond and optimally placed to be activated by endogenous IP3 and to regulate Ca2+ entry. IP3 receptors mediate Ca2+ release from the endoplasmic reticulum. Here the authors show that only a small fraction of IP3 receptors initiate Ca2+ signals; these immobile IP3 receptors adjacent to the plasma membrane are optimally placed to control STIM1-dependent Ca2+ entry.