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Ca2+ signals initiate at immobile IP3 receptors adjacent to ER-plasma membrane junctions.

ABSTRACT: IP3 receptors (IP3Rs) release Ca2+ from the ER when they bind IP3 and Ca2+. The spatial organization of IP3Rs determines both the propagation of Ca2+ signals between IP3Rs and the selective regulation of cellular responses. Here we use gene editing to fluorescently tag endogenous IP3Rs, and super-resolution microscopy to determine the geography of IP3Rs and Ca2+ signals within living cells. We show that native IP3Rs cluster within ER membranes. Most IP3R clusters are mobile, moved by diffusion and microtubule motors. Ca2+ signals are generated by a small population of immobile IP3Rs. These IP3Rs are licensed to respond, but they do not readily mix with mobile IP3Rs. The licensed IP3Rs reside alongside ER-plasma membrane junctions where STIM1, which regulates store-operated Ca2+ entry, accumulates after depletion of Ca2+ stores. IP3Rs 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.

SUBMITTER: Thillaiappan NB 

PROVIDER: S-EPMC5686115 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Ca<sup>2+</sup> signals initiate at immobile IP<sub>3</sub> receptors adjacent to ER-plasma membrane junctions.

Thillaiappan Nagendra Babu NB   Chavda Alap P AP   Tovey Stephen C SC   Prole David L DL   Taylor Colin W CW  

Nature communications 20171115 1

IP<sub>3</sub> receptors (IP<sub>3</sub>Rs) release Ca<sup>2+</sup> from the ER when they bind IP<sub>3</sub> and Ca<sup>2+</sup>. The spatial organization of IP<sub>3</sub>Rs determines both the propagation of Ca<sup>2+</sup> signals between IP<sub>3</sub>Rs and the selective regulation of cellular responses. Here we use gene editing to fluorescently tag endogenous IP<sub>3</sub>Rs, and super-resolution microscopy to determine the geography of IP<sub>3</sub>Rs and Ca<sup>2+</sup> signals within  ...[more]

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