title: Calcium-activated proteolysis of intracellular domains in the cell adhesion molecules NCAM and N-cadherin.
abstract: One of the consequences of increased intracellular calcium in response to a variety of physiological stimuli is the calcium activation of cytosolic proteases. Unlike lysosomal proteases with broad specificity, these calcium-activated neutral proteases show limited proteolysis of a restricted set of substrate proteins suggesting they may play a regulatory role in cellular physiology. In this study we show that the neural cell adhesion molecules NCAM-180 and N-cadherin are substrates for such endogenous calcium-activated neutral proteases. In contrast, a third neural cell adhesion molecule G4/L1 was not susceptible to calcium-activated proteolysis. The threshold for activation of NCAM and N-cadherin proteolysis is in the micromolar range of calcium suggesting that NCAM and N-cadherin are substrates for a mu-type calpain (calpain I). The site recognized by this protease is within intracellular domains of NCAM-180 and N-cadherin which are important for their interaction with cytoskeletal components. These results suggest that calcium-activated proteolysis at these sites in vivo could disrupt the linkage between extracellular ligand binding to these adhesion molecules and the normal intracellular effectors of such extracellular binding events.
authors.affiliation: Department of Physiology and Neurobiology, University of Connecticut, Storrs 06269-3042.
authors.forename: J
authors.initials: J
authors.lastname: Covault
authors.forename: Q Y
authors.initials: QY
authors.lastname: Liu
authors.forename: S
authors.initials: S
authors.lastname: el-Deeb
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002118:Calcium / Q000502:physiology*; D002154:Calpain / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002645:Chickens; D010450:Endopeptidases / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D015151:Immunoblotting; D008970:Molecular Weight
chemical_list: D015820:Cadherins; D015816:Cell Adhesion Molecules, Neuronal; D010450:Endopeptidases; D002154:Calpain; D002118:Calcium