Arcadlin is a neural activity-regulated cadherin involved in long term potentiation

Neural activity results in long term changes that underlie synaptic plastic ity. To examine the molecular basis of activity-dependent plasticity, we ha ve used differential cloning techniques to identify genes that are rapidly induced in brain neurons by synaptic activity. Here, we identify a novel ca dherin molecule Arcadlin (activity-regulated cadherin-like protein), arcadl in mRNA is rapidly and transiently induced in hippocampal granule cells by seizures and by N-methyl-D-aspartate-dependent synaptic activity in long te rm potentiation. The extracellular domain of Arcadlin is most homologous to protocadherin-8; however, the cytoplasmic region is distinct from that of any cadherin family member. Arcadlin protein is expressed at the synapses a nd shows a hemophilic binding activity in a Ca2+-dependent manner, Furtherm ore, application of Arcadlin antibody reduces excitatory postsynaptic poten tial amplitude and blocks long term potentiation in hippocampal slices. Its close homology with cadherins, its rapid inducibility by neural activity, and its involvement in synaptic transmission suggest that Arcadlin may play an important role in activity-induced synaptic reorganization underlying l ong term memory.