NMDA-dependent proteolysis of presynaptic adhesion molecule L1 in the hippocampus by neuropsin.
Synaptic plasticity requires an activity-dependent, rapid, and long-lasting modification of synaptic character, including morphology and coupling strength. Here we show that a serine protease, neuropsin, directly and specifically modifies the synaptic adhesion molecule L1, which was localized to the presynaptic site of the asymmetric synapse in the mouse hippocampus. Increased neural activity triggered the rapid, transient activation of the precursor form of neuropsin in an NMDA receptor-dependent manner. The activated neuropsin immediately cleaved L1 and released a neuropsin-specific extracellular 180 kDa fragment. This neuropsin-specific L1-cleaving system is involved in NMDA receptor-dependent synaptic plasticity, such as the Schaffer collateral long-term potentiation.
Matsumoto-Miyai
Kazumasa
K
Division of Structural Cell Biology, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan. kmatsumo@bs.aist-nara.ac.jp
Ninomiya
Ayako
A
Yamasaki
Hironobu
H
Tamura
Hideki
H
Nakamura
Yukiko
Y
Shiosaka
Sadao
S
D000818:Animals; D002460:Cell Line; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology; D007610:Kallikreins / Q000378:metabolism*; D017774:Long-Term Potentiation; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology*; D039842:Neural Cell Adhesion Molecule L1 / Q000032:analysis / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism; D017966:Pyramidal Cells / Q000201:enzymology / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism
D039842:Neural Cell Adhesion Molecule L1; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; C094799:KLK8 protein, human; D007610:Kallikreins