| First Author | Arratia LM | Year | 2024 |
| Journal | Sci Rep | Volume | 14 |
| Issue | 1 | Pages | 6761 |
| PubMed ID | 38514708 | Mgi Jnum | J:380242 |
| Mgi Id | MGI:7615720 | Doi | 10.1038/s41598-024-57117-8 |
| Citation | Arratia LM, et al. (2024) Experimental and computational evidence that Calpain-10 binds to the carboxy terminus of Na(V)1.2 and Na(V)1.6. Sci Rep 14(1):6761 |
| abstractText | Voltage-gated sodium channels (Na(V)) are pivotal proteins responsible for initiating and transmitting action potentials. Emerging evidence suggests that proteolytic cleavage of sodium channels by calpains is pivotal in diverse physiological scenarios, including ischemia, brain injury, and neuropathic pain associated with diabetes. Despite this significance, the precise mechanism by which calpains recognize sodium channels, especially given the multiple calpain isoforms expressed in neurons, remains elusive. In this work, we show the interaction of Calpain-10 with Na(V)'s C-terminus through a yeast 2-hybrid assay screening of a mouse brain cDNA library and in vitro by GST-pulldown. Later, we also obtained a structural and dynamic hypothesis of this interaction by modeling, docking, and molecular dynamics simulation. These results indicate that Calpain-10 interacts differentially with the C-terminus of Na(V)1.2 and Na(V)1.6. Calpain-10 interacts with Na(V)1.2 through domains III and T in a stable manner. In contrast, its interaction with Na(V)1.6 involves domains II and III, which could promote proteolysis through the Cys-catalytic site and C2 motifs. |
