RYR3

RyR3, or ryanodine receptor 3, is an intracellular calcium release channel located on the sarcoplasmic reticulum in muscle cells and the endoplasmic reticulum in nonmuscle cells. It is encoded by the RYR3 gene and is one of three ryanodine receptor isoforms (RyR1, RyR2, and RyR3). The channel forms tetramers and mediates calcium-induced calcium release in response to cytosolic Ca2+ and other ligands.

Expression of RyR3 is widely distributed, with particularly high levels in the brain (including the hippocampus, cortex, and cerebellum) and in various smooth muscle tissues; it is also found at lower levels in cardiac muscle. At the cellular level, RyR3 resides in the junctional sarcoplasmic/endoplasmic reticulum where it forms macromolecular complexes with regulatory proteins such as triadin, junctin, and calsequestrin, and is stabilized by binding proteins like FKBP.

Function and regulation of RyR3 involve gating that is modulated by cytosolic Ca2+, luminal Ca2+, ATP, Mg2+, and pharmacological ligands such as ryanodine. Phosphorylation by PKA or CaMKII and interactions with accessory proteins can modify the channel’s open probability. RyR3 can participate in homotetrameric channels or in heterotetramers with other RyR isoforms in tissues expressing multiple isoforms.

Physiological and clinical significance: in neurons, RyR3 contributes to dendritic Ca2+ signaling and synaptic plasticity, influencing learning and memory. Dysregulation of RyR3-mediated Ca2+ release has been explored in various neuropsychiatric and neurodegenerative contexts, though the precise role remains an active area of research. Animal studies using RYR3 knockout or knockdown models have shown effects on hippocampal Ca2+ signaling and plasticity.

See also: RYR1, RYR2.