Presence of up-stream and downstream components of a mitogen-activated protein kinase pathway in the PSD of the rat forebrain.

We previously reported the presence of Erk2 type mitogen-activated protein kinase (MAPK) and enrichment of its substrates in the post-synaptic density (PSD) fraction, and suggested a role for MAPK in the synaptic transmission and its modulation [Suzuki, T., Okumura-Noji, K., Nishida, E., ERK2-type mitogen-activated protein kinase (MAPK) and its substrates in post-synaptic density fractions from the rat brain, Neurosci. Res., 22 (1995) 277-285.]. In this paper, synaptic localization of the upstream and downstream components of a MAPK cascade was examined. We found that RSK1, Sos1, N-Shc 66 kDa, N-Shc 52 kDa, and Grb2 were present in the PSD fraction, and cPLA(2) was present in the synaptic plasma membrane fraction. RSK2, Sos2, and N-Shc 46 kDa were not present in the PSD fraction. Post-synaptic localization of RSK1 and Sos1 was confirmed by immunohistochemical examination at the electron microscopic level: the two immunoreactivities were localized in the PSDs, both in the spines and dendrites. These results suggest that all the MAPK cascade components examined were associated with PSD or the synaptic plasma membrane, suggesting the role(s) of the MAPK cascade for synaptic transmission and its regulation at post-synaptic sites.