A Kinase to Remember: Dual Roles for MAP Kinase in Long-Term Memory

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The selective down-regulation of the transmembrane apCAM isoform has been proposed to remove inhibitory constraints on neuronal outgrowth by promoting the disassembly of adhesive contacts between sensory neuron processes that normally inhibit growth. However, any role that the internalization of the transmembrane form of apCAM plays in the relief of inhibitory constraints on synaptic reorganization must be reconciled with the continued presence of the GPI-linked form of apCAM. Clearly, the ratio of transmembrane to GPI-linked apCAM may be important. One interesting idea raised by Kandel and colleagues is that the spatial distributions of the transmembrane and GPI-linked isoforms may be distinct, with the transmembrane form localized to the neurite processes that mediate homophilic interactions, and the GPI-linked form localized to the synaptic region that mediates heterophilic (sensory to motor neuron) interactions. If this were the case, the selective removal of the transmembrane form would alter the relative levels of the two apCAM isoforms in favor of the GPI-linked form, thereby promoting outgrowth and association with the postsynaptic neuron.These new findings in Aplysia may have important implications for other organisms including insects and mammals. Although MAP kinase has not yet been shown to be critical for learning and memory in vertebratesMartin et al. 1997xMartin, K.C, Michael, D, Rose, J.C, Barad, M, Casadio, A, Zhu, H, and Kandel, E.R. Neuron. 1997; 18Abstract | Full Text | Full Text PDF | Scopus (411)See all ReferencesMartin et al. 1997 demonstrate that exposure of hippocampal slices to forskolin, an activator of adenylate cyclase, leads to MAP kinase phosphorylation within the nucleus in hippocampal pyramidal neurons. This is consistent with the finding that stimuli that trigger LTP in the hippocampus can induce MAP kinase activity (Thomas et al. 1994xThomas, K.L, Laroche, S, Errington, M.L, Bliss, T.V.P, and Hunt, S.P. Neuron. 1994; 13: 737–745Abstract | Full Text PDF | PubMed | Scopus (150)See all ReferencesThomas et al. 1994), and raises the possibility that PKA is important for the activation of MAP kinase, which could in turn mediate events that are critical for the establishment and maintenance of LTP. Since CAMs have already been demonstrated to play a role in the regulation of synaptic potentiation in Aplysia, Drosophila, and mice, it will be important to determine whether features of MAP kinase regulation of CAM expression observed in Aplysia represent a general mechanism of synaptic facilitation that is conserved through evolution.