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Licensed Unlicensed Requires Authentication Published by De Gruyter May 15, 2013

Does extracellular proteolysis control mammalian cognition?

Hideki Tamura, Yasuyuki Ishikawa and Sadao Shiosaka


Recent advances in neuroscience techniques for analyzing synaptic functions, have revealed that even in a fully developed nervous system, dynamic structural changes in synapses can modify a variety of interactions between the presynaptic and postsynaptic neuron. Accumulating evidence suggests that extracellular proteases are involved in the structural modification of synapses through various pathways, including proteolytic cleavage at specific amino acid residues of the extracellular matrix proteins, cell adhesion molecules, and neurotrophic factors. Limited proteolysis induces changes in the properties of substrate proteins or releases functional domains (such as ligands) of the substrate proteins, which activate a signal transduction cascade, and hence could serve to initiate a variety of physiological functions. Such morphological and functional synaptic plasticity might underlie cognitive processes, including learning and memory in animals and humans. Here, we review potential molecular mechanisms of cognition-related focal proteolysis in the hippocampus. In addition, we developed a novel screening method to identify the physiological substrate for proteases.

Corresponding authors: Hideki Tamura and Sadao Shiosaka, Laboratory of Functional Neuroscience, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630–0192, Japan

This work was supported by JSPS KAKENHI Grant No. 24500439 to HT, No. 23700449 to YI, No. 20300128 to SS, and Japan Science and Technology Agency (JST) CREST program to SS. We thank Dr. Zu-Lin Chen (The Rockefeller University) and Professor Robert Pawlak (University of Exeter) for their valuable comments.


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Received: 2013-3-12
Accepted: 2013-4-14
Published Online: 2013-05-15
Published in Print: 2013-08-01

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