MUTATION IN THE PHOSPHORYLATION SITES OF MAP KINASE BLOCKS LEARNING-RELATED INTERNALIZATION OF APCAM IN APLYSIA SENSORY NEURONS

The synaptic growth that accompanies 5-HT-induced long-term facilitati on of the sensory to motor neuron connection in Aplysia is associated with the internalization of apCAM at the surface membrane of the senso ry neuron. We have now used epitope tags to examine the fate of each o f the two apCAM isoforms (membrane bound and GPI-linked) and find that only the transmembrane form is internalized. This internalization can be blocked by overexpression of transmembrane constructs with a singl e point mutation in the two MAPK consensus sites, as well as by inject ion of a specific MAPK antagonist into sensory neurons. These data sug gest MAPK phosphorylation at the membrane is important for the interna lization of apCAMs and, thus, may represent an early regulatory step i n the growth of new synaptic connections that accompanies long-term fa cilitation.