Roles of proteases on cell-to-cell adhesion and deadhesion

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Some proteases have been suggested to be related to cell dynamics in such processes as cell death, cell migration, cell-to-cell adhesion and deadhesion, and neural process elongation, pathfinding and axonal rearrangement, we postulated that (a) novel protease (s) might be released from neurons and relate to various cell dynamics described above.Neuropsin was cloned from the mouse brain and was shown to be localized in mouse hippocampal pyramidal neurons and also epidermal keratinocytes. Recombinant neuropsin effectively cleaved fibronectin which is a major ECM protein expressed in variety of tissues. The specific cleavage by recombinant neuropsin as shown in the present study might directly affect fibronectin's functions as a cell adhesion molecule, because the N-terminal 5 FnI domains contain the main fibrin-binding site. Cell migration and cell atachment activity were analyzed with model system using CHO cell which expressing alpha5beta1 integlin. Recombinant neuropsin effectively decreased these activity when fibronectin was used as cell adhesion molecule.Neuropsin knock-out mouse was made and histological, bichemical, physiological and behavioral analysis is now in progress.