| First Author | Kim J | Year | 2011 |
| Journal | J Neurochem | Volume | 119 |
| Issue | 5 | Pages | 945-56 |
| PubMed ID | 21910732 | Mgi Jnum | J:178371 |
| Mgi Id | MGI:5298270 | Doi | 10.1111/j.1471-4159.2011.07479.x |
| Citation | Kim J, et al. (2011) Characterization of nectin processing mediated by presenilin-dependent gamma-secretase. J Neurochem 119(5):945-56 |
| abstractText | Nectins play an important role in forming various intercellular junctions including synapses. This role is regulated by several secretases present at intercellular junctions. We have investigated presenilin (PS)-dependent secretase-mediated processing of nectins in PS1 KO cells and primary hippocampal neurons. The loss of PS1/gamma-secretase activity delayed the processing of nectin-1 and caused the accumulation of its full-length and C-terminal fragments. Over-expression of PS2 in PS1 KO cells compensated for the loss of PS1, suggesting that PS2 also has the ability to regulate nectin-1 processing. In mouse brain slices, a pronounced increase in levels of 30 and 24 kDa C-terminal fragments in response to chemical long-term potentiation was observed. The mouse brain synaptosomal fractionation study indicated that nectin-1 localized to post-synaptic and preferentially pre-synaptic membranes and that shedding occurs in both compartments. These data suggest that nectin-1 shedding and PS-dependent intramembrane cleavage occur at synapses, and is a regulated event during conditions of synaptic plasticity in the brain. Point mutation analysis identified several residues within the transmembrane domain that play a critical role in the positioning of cleavage sites by ectodomain sheddases. Nectin-3, which forms hetero-trans-dimers with nectin-1, also undergoes intramembrane cleavage mediated by PS1/gamma-secretase, suggesting that PS1/gamma-secreatse activity regulates synapse formation and remodeling by nectin processing. |
