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

Curcic, Sanja; Erkan‐Candag, Hazel; Pilic, Johannes; Malli, Roland; Wiedner, Patrick; Tiapko, Oleksandra

doi:10.1016/j.ceca.2022.102670

Cited by 10 publications

(4 citation statements)

References 47 publications

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“…Of particular interest are findings showing that TRPC3 binds to IP 3 R ( Yuan et al, 2003 ; Adebiyi et al, 2012 ) through its calmodulin/IP 3 R binding domain ( Zhang et al, 2001 ). This C-terminus motif impacts channel gating ( Wedel et al, 2003 ) and presumptively the concomitant Ca 2+ influx needed to initiate or sustain SR Ca 2+ waves generation ( Curcic et al, 2022 ). Note, TRPC1 also been alluded to interact with IP 3 Rs although findings remain limited ( Yuan et al, 2003 ).…”

Section: Ca 2+ Permeable Pores and Ca 2+...mentioning

confidence: 99%

TRP channels: a provocative rationalization for local Ca2+ control in arterial tone development

El-Lakany,

Welsh

2024

Front. Physiol.

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Arterial networks are controlled by the consolidated output of stimuli that set “how much” (magnitude) and “where” (distribution) blood flow is delivered. While notable changes in magnitude are tied to network wide responses, altered distribution often arises from focal changes in tone, whose mechanistic foundation remains unclear. We propose herein a framework of focal vasomotor contractility being controlled by pharmacomechanical coupling and the generation of Ca2+ waves via the sarcoplasmic reticulum. We argue the latter is sustained by receptor operated, transient receptor potential (TRP) channels through direct extracellular Ca2+ influx or indirect Na+ influx, reversing the Na+/Ca2+ exchanger. We view this focal regulatory mechanism as complementary, but not redundant with, electromechanical coupling in the precision tuning of blood flow delivery.

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Section: Ca 2+ Permeable Pores and Ca 2+...mentioning

confidence: 99%

TRP channels: a provocative rationalization for local Ca2+ control in arterial tone development

El-Lakany,

Welsh

2024

Front. Physiol.

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“…Additionally, the functional association between mGluR1 and TRPC3 is thought to be important for the induction of long-term depression in the cerebellum [ 39 ]. TRPC3-mediated Ca 2+ entry has been linked to control of IP3R activity at endoplasmic reticulum–plasma membrane junctions in HEK293T cells to regulate Ca 2+ homeostasis [ 40 ]. IP3R undergoes biphasic regulation by Ca 2+ ions and elevations in cytosolic Ca 2+ mediated by TRPC3 inhibit IP3R activity [ 40 ].…”

Section: The Role Of Trpc3 In Normal Physiology and Human Diseasementioning

confidence: 99%

“…TRPC3-mediated Ca 2+ entry has been linked to control of IP3R activity at endoplasmic reticulum–plasma membrane junctions in HEK293T cells to regulate Ca 2+ homeostasis [ 40 ]. IP3R undergoes biphasic regulation by Ca 2+ ions and elevations in cytosolic Ca 2+ mediated by TRPC3 inhibit IP3R activity [ 40 ]. Given the importance of IP3R signalling in Purkinje cells [ 41 ] and its activation downstream of mGlur1 ( Figure 3 ), it is conceivable that TRPC3 may regulate IP3R function in Purkinje cells, but this remains to be shown experimentally.…”

Section: The Role Of Trpc3 In Normal Physiology and Human Diseasementioning

confidence: 99%

Modulation and Regulation of Canonical Transient Receptor Potential 3 (TRPC3) Channels

Cole,

Becker

2023

Cells

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Canonical transient receptor potential 3 (TRPC3) channel is a non-selective cation permeable channel that plays an essential role in calcium signalling. TRPC3 is highly expressed in the brain and also found in endocrine tissues and smooth muscle cells. The channel is activated directly by binding of diacylglycerol downstream of G-protein coupled receptor activation. In addition, TRPC3 is regulated by endogenous factors including Ca2+ ions, other endogenous lipids, and interacting proteins. The molecular and structural mechanisms underlying activation and regulation of TRPC3 are incompletely understood. Recently, several high-resolution cryogenic electron microscopy structures of TRPC3 and the closely related channel TRPC6 have been resolved in different functional states and in the presence of modulators, coupled with mutagenesis studies and electrophysiological characterisation. Here, we review the recent literature which has advanced our understanding of the complex mechanisms underlying modulation of TRPC3 by both endogenous and exogenous factors. TRPC3 plays an important role in Ca2+ homeostasis and entry into cells throughout the body, and both pathological variants and downstream dysregulation of TRPC3 channels have been associated with a number of diseases. As such, TRPC3 may be a valuable therapeutic target, and understanding its regulatory mechanisms will aid future development of pharmacological modulators of the channel.

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“…These ionic transporters are also present on the membranes of intracellular organelles, such as the endoplasmic/sarcoplasmic reticulum, the mitochondria, and the nucleus [16,17]. In addition, calcium micro-and nanodomains are formed at the inner side of the mouth of a transporter that contributes to intracellular calcium release, uptake, and signaling [18][19][20][21][22]. These micro/nanodomains enable the cell to use calcium in a specific part of the cell [18].…”

Section: Introductionmentioning

confidence: 99%

Calcium Homeostasis, Transporters, and Blockers in Health and Diseases of the Cardiovascular System

Bkaily

Jacques

2023

IJMS

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Calcium is a highly positively charged ionic species. It regulates all cell types’ functions and is an important second messenger that controls and triggers several mechanisms, including membrane stabilization, permeability, contraction, secretion, mitosis, intercellular communications, and in the activation of kinases and gene expression. Therefore, controlling calcium transport and its intracellular homeostasis in physiology leads to the healthy functioning of the biological system. However, abnormal extracellular and intracellular calcium homeostasis leads to cardiovascular, skeletal, immune, secretory diseases, and cancer. Therefore, the pharmacological control of calcium influx directly via calcium channels and exchangers and its outflow via calcium pumps and uptake by the ER/SR are crucial in treating calcium transport remodeling in pathology. Here, we mainly focused on selective calcium transporters and blockers in the cardiovascular system.

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

Cited by 10 publications

References 47 publications

TRP channels: a provocative rationalization for local Ca2+ control in arterial tone development

TRP channels: a provocative rationalization for local Ca2+ control in arterial tone development

Modulation and Regulation of Canonical Transient Receptor Potential 3 (TRPC3) Channels

Calcium Homeostasis, Transporters, and Blockers in Health and Diseases of the Cardiovascular System

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