| First Author | Grillo MA | Year | 2019 |
| Journal | Mol Neurobiol | Volume | 56 |
| Issue | 1 | Pages | 525-534 |
| PubMed ID | 29730765 | Mgi Jnum | J:325842 |
| Mgi Id | MGI:6873800 | Doi | 10.1007/s12035-018-1080-2 |
| Citation | Grillo MA, et al. (2019) Control of Neuronal Ryanodine Receptor-Mediated Calcium Signaling by Calsenilin. Mol Neurobiol 56(1):525-534 |
| abstractText | Calsenilin is a calcium ion (Ca(2+))-binding protein involved in regulating the intracellular concentration of Ca(2+), a second messenger that controls multiple cellular signaling pathways. The ryanodine receptor (RyR) amplifies Ca(2+) signals entering the cytoplasm by releasing Ca(2+) from endoplasmic reticulum (ER) stores, a process termed calcium-induced calcium release (CICR). Here, we describe a novel mechanism, in which calsenilin controls the activity of neuronal RyRs. We show calsenilin co-localized with RyR2 and 3 in the ER of mouse hippocampal and cortical neurons using immunocytochemistry. The underlying protein-protein interaction between calsenilin and the RyR was determined in mouse central nervous system (CNS) neurons using immunoprecipitation studies. The functional relevance of this interaction was assayed with single-channel electrophysiology. At low physiological Ca(2+) concentrations, calsenilin binding to the cytoplasmic face of neuronal RyRs decreased the RyR's open probability, while calsenilin increased the open probability at high physiological Ca(2+) concentrations. This novel molecular mechanism was studied further at the cellular level, where faster release kinetics of caffeine-induced Ca(2+) release were measured in SH-SY5Y neuroblastoma cells overexpressing calsenilin. The interaction between calsenilin and neuronal RyRs reveals a new regulatory mechanism and possibly a novel pharmacological target for the control of Ca(2+) release from intracellular stores. |
