Calcium-activated proteolysis of intracellular domains in the cell adhesion molecules NCAM and N-cadherin

Brain Res Mol Brain Res. 1991 Aug;11(1):11-6. doi: 10.1016/0169-328x(91)90015-p.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cadherins / metabolism*
  • Calcium / physiology*
  • Calpain / metabolism
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Chickens
  • Endopeptidases / metabolism*
  • Enzyme Activation / physiology
  • Immunoblotting
  • Molecular Weight


  • Cadherins
  • Cell Adhesion Molecules, Neuronal
  • Endopeptidases
  • Calpain
  • Calcium