Reciprocal actions of NCAM and tPA via a Ras-dependent MAPK activation in rat hippocampal neurons.
In an attempt to identify the functions of neural cell adhesion molecule (NCAM) and tissue plasminogen activator (tPA) in hippocampal synaptic plasticity, we investigated the relationship between the two molecules by focusing on mitogen-activated protein kinase (MAPK), an essential enzyme in this process. NCAM clustering in cultured hippocampal neurons transiently induced MAPK within 10min. Moreover, soluble NCAM also induced a Ras-dependent MAPK activation. Conversely, MAPK activation led to an increase in the expressions of all three isoforms of NCAM. Treatment of neurons with tPA and plasminogen induced a Ras-dependent MAPK activation and tPA-plasmin degradation of NCAM was mediated in a MAPK-dependent manner. Soluble NCAM transiently inhibited tPA mRNA expression levels in a MAPK-dependent manner, while stimulation of MAPK alone induced tPA reduction in cells. These results collectively indicate that NCAM and tPA reciprocally act as important regulators in the modulation of synaptic plasticity via a Ras-MAPK-involved signaling pathway. In turn, MAPK activation may cause tPA degradation or a decrease in expression to promote synaptic plasticity.
Son
Hyeon
H
Department of Biochemistry, Hanyang University College of Medicine, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791, South Korea.
Seuk Kim
Jin
J
Mogg Kim
Jung
J
Lee
Sang-Hun
SH
Lee
Yong-Sung
YS
D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D007700:Kinetics; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D019006:Neural Cell Adhesion Molecules / Q000494:pharmacology / Q000502:physiology*; D009474:Neurons / Q000201:enzymology / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology*; D051381:Rats; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*
D019006:Neural Cell Adhesion Molecules; D010958:Plasminogen; D020928:Mitogen-Activated Protein Kinases; D010959:Tissue Plasminogen Activator; D016283:Proto-Oncogene Proteins p21(ras)