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J Biol Chem, Vol. 274, Issue 27, 19473-19479, July 2, 1999

Arcadlin Is a Neural Activity-regulated Cadherin Involved in Long Term Potentiation

Kanato Yamagata, Katrin I. Andreasson^¶, Hiroko Sugiura, Eiichi Maru, Muller Dominique^**, Yasuyuki Irie, Naomasa Miki, Yokichi Hayashi^§§, Masatomo Yoshioka^¶¶, Kenya Kaneko^¶¶, Hiroshi Kato^¶¶, and Paul F. Worley^¶

From the  Department of Molecular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, Fuchu 183, Japan, the ^¶ Department of Neuroscience and Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, the  Department of Physiology II, Nippon Medical University School of Medicine, Tokyo 113, Japan, the ^** Department of Pharmacology, Centre Medical Universitaire, CH-1211 Geneve 4, Switzerland, the  Department of Pharmacology I, Osaka University School of Medicine, Suita 565, Japan, ^§§ Nagano Nursing University, Komagane 399-41, Japan, and the ^¶¶ Department of Physiology II, Yamagata University School of Medicine, Yamagata 990-23, Japan

Neural activity results in long term changes that underlie synaptic plasticity. To examine the molecular basis of activity-dependent plasticity, we have used differential cloning techniques to identify genes that are rapidly induced in brain neurons by synaptic activity. Here, we identify a novel cadherin molecule Arcadlin (activity-regulated cadherin-like protein). arcadlin mRNA is rapidly and transiently induced in hippocampal granule cells by seizures and by N-methyl-D-aspartate-dependent synaptic activity in long term 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 and shows a homophilic binding activity in a Ca²⁺-dependent manner. Furthermore, application of Arcadlin antibody reduces excitatory postsynaptic potential 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 long term memory.

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Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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