Ryanodine receptor 3 (RyR3) (encoded by the RYR3 gene) is an intracellular calcium release channel expressed in brain, smooth muscle, and diaphragm. In the nervous system, RyR3 is enriched in the hippocampus and striatum, where it modulates calcium-dependent synaptic plasticity and learning.
RyR3 is the third isoform of the ryanodine receptor family, forming a homotetrameric ER calcium release channel of similar size to RyR1 and RyR2[1]. Each subunit is 4,872 amino acids. RyR3 has the most restricted tissue distribution of the three RyR isoforms but is notably enriched in specific brain regions, particularly the hippocampus CA1 region, striatum, and thalamus[2]. RyR3 knockout mice show enhanced hippocampal LTP and impaired spatial learning, suggesting RyR3 normally provides a brake on calcium signaling that refines plasticity. [1]
| | | [2]
|---|---|
| Protein Name | Ryanodine Receptor 3 (RyR3) |
| Gene | RYR3 |
| UniProt ID | Q15413 |
| Molecular Weight | ~552 kDa (monomer), ~2.2 MDa (tetramer) |
| Length | 4,872 amino acids |
| Subcellular Localization | ER membrane |
| Function | Intracellular Ca²⁺ release channel |
RyR3 modulates intracellular calcium dynamics in specific neuronal populations[2]:
RyR3 differs from RyR1 and RyR2 in several functional aspects[1]:
RyR3 dysregulation affects processes impaired in neurodegenerative diseases[3]:
| Interactor | Type | Function |
|---|---|---|
| FKBP12 | Stabilizer | Calstabin-1; stabilizes closed channel state |
| Calmodulin | Modulator | Calcium-dependent regulation |
| RyR1 | Hetero-oligomer | May form heteromeric channels in brain |
| RyR2 | Co-expressed | Complementary ER calcium release in hippocampus |
Bhatt DG et al. Ryanodine receptors in the nervous system (2014). 2014. ↩︎
Bhatt DG et al. Calcium signaling and Alzheimer's disease (2017). 2017. ↩︎