| First Author | Kim J | Year | 2010 |
| Journal | J Biol Chem | Volume | 285 |
| Issue | 30 | Pages | 22919-26 |
| PubMed ID | 20501653 | Mgi Jnum | J:165836 |
| Mgi Id | MGI:4838516 | Doi | 10.1074/jbc.M110.126649 |
| Citation | Kim J, et al. (2010) Activity-dependent alpha-cleavage of nectin-1 is mediated by a disintegrin and metalloprotease 10 (ADAM10). J Biol Chem 285(30):22919-26 |
| abstractText | Nectin-1 is known to undergo ectodomain shedding by alpha-secretase and subsequent proteolytic processing by gamma-secretase. How secretase-mediated cleavage of nectin-1 is regulated in neuronal cells and how nectin-1 cleavage affects synaptic adhesion is poorly understood. We have investigated alpha-and gamma-secretase-mediated processing of nectin-1 in primary cortical neurons and identified which protease acts as a alpha-secretase. We report here that NMDA receptor activation, but not stimulation of AMPA or metabotropic glutamate receptors, resulted in robust alpha- and gamma-secretase cleavage of nectin-1 in mature cortical neurons. Cleavage of nectin-1 required influx of Ca(2+) through the NMDA receptor, and activation of calmodulin, but was not dependent on calcium/calmodulin-dependent protein kinase II (CaMKII) activation. We found that ADAM10 is the major secretase responsible for nectin-1 ectodomain cleavage in neurons and the brain. These observations suggest that alpha- and gamma-secretase processing of nectin-1 is a Ca(2+)/calmodulin-regulated event that occurs under conditions of activity-dependent synaptic plasticity and ADAM10 and gamma-secretase are responsible for these cleavage events. |
