Loading…

TRPC3 governs the spatiotemporal organization of cellular Ca2+ signatures by functional coupling to IP3 receptors

•TRPC3 shares a common Ca2+ signaling microdomain with IP3 receptors.•TRPC3-mediated Ca2+ entry suppresses microdomain Ca2+ spiking and oscillations.•TRPC3 is transiently targeted into ER-plasma membrane junctions to communicate with IP3 receptors in a dynamic manner.•TRPC3 activity states govern sp...

Full description

Saved in:
Bibliographic Details
Published in:Cell calcium (Edinburgh) 2022-12, Vol.108, p.102670, Article 102670
Main Authors: Curcic, Sanja, Erkan-Candag, Hazel, Pilic, Johannes, Malli, Roland, Wiedner, Patrick, Tiapko, Oleksandra, Groschner, Klaus
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:•TRPC3 shares a common Ca2+ signaling microdomain with IP3 receptors.•TRPC3-mediated Ca2+ entry suppresses microdomain Ca2+ spiking and oscillations.•TRPC3 is transiently targeted into ER-plasma membrane junctions to communicate with IP3 receptors in a dynamic manner.•TRPC3 activity states govern spatiotemporal Ca2+ signaling signatures. Communication between TRPC channels and IP3 receptors (IP3R) is considered pivotal in the generation of spatiotemporal Ca2+signaling patterns. Here we revisited the role of TRPC3-IP3R coupling for local Ca2+ signaling within TRPC3-harbouring micro/nanodomains using R-GECO as a reporter, fused to the channel´s C-terminus. Cytoplasmic Ca2+ changes at TRPC3 originated from both the entry of Ca2+ through the TRPC channel and Ca2+ mobilization via IP3R. Local Ca2+ changes at TRPC3 channels expressed in HEK293 cells were predominantly biphasic with IP3R-dependent initial Ca2+ transients, while exclusively monophasic signals were recorded when all three IP3R isoforms were lacking. Abrogation of Ca2+ entry through TRPC3 by point mutations, which impair Ca2+ permeability (E630Q), cation permeation (E630K), or DAG sensitivity (G652A), promoted microdomain Ca2+ oscillations. Ca2+ signals at E630Q, E630K, and G652A channels featured initial Ca2+ transients along with oscillatory activity. Similarly, when extracellular Ca2+ was omitted, IP3R-mediated Ca2+ transients and Ca2+ oscillations were promoted at the cytoplasmic face of wild-type TRPC3 channels. By contrast, oscillations, as well as initial Ca2+ transients, were virtually lacking, when the TRPC3 channels were sensitized by preexposure to low-level PLC activity. TIRF imaging provided evidence for dynamic colocalization of TRPC3 and IP3R. We suggest that TRPC3-mediated Ca2+ entry controls IP3R activity at ER-PM junctions to determine Ca2+ signaling signatures and enable specificity of downstream signaling. [Display omitted]
ISSN:0143-4160
1532-1991
1532-1991
DOI:10.1016/j.ceca.2022.102670