Hepatocyte growth factor promotes the number of PSD-95 clusters in young hippocampal neurons.
Hepatocyte growth factor (HGF) and its receptor are expressed in various regions of the brain and have protective effects against excitotoxic injuries. However, their effects on synapse formation remain to be elucidated. To determine whether HGF has the ability to alter synaptic function during development, we investigated changes in the number of synapse detected by double immunostaining for NMDA receptor subunits and a presynaptic marker in cultured young hippocampal neurons. Whereas application of HGF increased the number of cluster of synapsin, a presynaptic protein, the clusters of NMDA receptor subunits NR1 and NR2B were not altered. Interestingly, colocalization of PSD-95, a scaffolding protein of the receptor, with synapsin was increased by HGF treatment without a change in the total amount of it. In addition, we investigated the expression of surface NMDA receptor, neuroligin, and neurexin, which were assessed by use of a cell-surface biotinylation assay. The application of HGF did not change the surface expression of these proteins. Furthermore, we determined the release of glutamate in response to depolarization. Treatment with HGF promoted depolarization-evoked release of glutamate. These results suggest that HGF modulates the expression of the scaffolding protein of the NMDA receptor at the synapse and promotes maturation of excitatory synapses in young hippocampal neurons.
Department of Molecular and Cellular Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Midori
M
Nakano
Norio
N
Takagi
Keiko
K
Takagi
Hiroshi
H
Funakoshi
Kunio
K
Matsumoto
Toshikazu
T
Nakamura
Satoshi
S
Takeo
D000818:Animals; D019921:Biotinylation; D002478:Cells, Cultured; D000076122:Disks Large Homolog 4 Protein; D004622:Embryo, Mammalian; D018698:Glutamic Acid / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects*; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D016704:Synapsins / Q000378:metabolism*
D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D016704:Synapsins; D018698:Glutamic Acid; D017228:Hepatocyte Growth Factor