Activity-dependent proteolytic cleavage of cell adhesion molecules regulates excitatory synaptic development and function

Neurosci Res. 2017 Mar;116:60-69. doi: 10.1016/j.neures.2016.12.003. Epub 2016 Dec 10.


Activity-dependent remodeling of neuronal connections is critical to nervous system development and function. These processes rely on the ability of synapses to detect neuronal activity and translate it into the appropriate molecular signals. One way to convert neuronal activity into downstream signaling is the proteolytic cleavage of cell adhesion molecules (CAMs). Here we review studies demonstrating the mechanisms by which proteolytic processing of CAMs direct the structural and functional remodeling of excitatory glutamatergic synapses during development and plasticity. Specifically, we examine how extracellular proteolytic cleavage of CAMs switches on or off molecular signals to 1) permit, drive, or restrict synaptic maturation during development and 2) strengthen or weaken synapses during adult plasticity. We will also examine emerging studies linking improper activity-dependent proteolytic processing of CAMs to neurological disorders such as schizophrenia, brain tumors, and Alzheimer's disease. Together these findings suggest that the regulation of activity-dependent proteolytic cleavage of CAMs is vital to proper brain development and lifelong function.

Keywords: Cell adhesion molecules; Neuronal activity; Proteolytic cleavage; Synaptic development; Synaptic plasticity.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / metabolism
  • Animals
  • Brain / growth & development
  • Brain / physiology*
  • Brain Neoplasms / metabolism
  • Cell Adhesion Molecules / metabolism*
  • Humans
  • Neuronal Plasticity
  • Neurons / metabolism
  • Proteolysis
  • Schizophrenia / metabolism
  • Synapses / physiology*


  • Cell Adhesion Molecules