Proteolytic Remodeling of the Synaptic Cell Adhesion Molecules (CAMs) by Metzincins in Synaptic Plasticity

Malgorzata Bajor,Leszek Kaczmarek

doi:10.1007/s11064-012-0919-6

Abstract

Cell adhesion molecules participate in the formation, maturation, function and plasticity of synaptic connections. The growing body of evidence indicates that in the regulation of the synaptic plasticity, in which these molecules play pivotal role, also the proteolytic processes are involved. This review focuses on extracellular proteolysis of the cell adhesion molecules by specific subgroup of the matrix metalloproteinases, a disintegrin and metalloproteases and a disintegrin and metalloproteinase with thrombospondin motifs, jointly referred to as metzincins, in driving coordinated synaptic structural and functional modifications underlying synaptic plasticity in the adult brain.

Highlights

After the initial establishment of neuronal connections during development, synapses remain highly dynamic and undergo activity-dependent changes in their efficacy and morphology
This review focuses on extracellular proteolysis of the cell adhesion molecules by specific subgroup of the matrix metalloproteinases, a disintegrin and metalloproteases and a disintegrin and metalloproteinase with thrombospondin motifs, jointly referred to as metzincins, in driving coordinated synaptic structural and functional modifications underlying synaptic plasticity in the adult brain
The ADAM10 driven processing in response to calcium influx via NMDA type glutamate receptor is required for the subsequent PS1/csecretase cleavage of N-cadherin, which leads to releasing of a cytoplasmic fragment

Summary

Introduction

After the initial establishment of neuronal connections during development, synapses remain highly dynamic and undergo activity-dependent changes in their efficacy and morphology. Cell adhesion molecules (CAMs) at the synapse mediate synaptic plasticity, the ability to change synaptic function, thought to underlie learning and memory, as well as implicated in a number of neuropsychiatric conditions. It is, still poorly understood how synaptic CAMs contribute to synapse formation and/or structure, and whether and/or how smaller groups of CAMs serve as minimal, functionally cooperative adhesive units upon which the structure is based [1]. A majority of these dynamic changes in the synaptic microenvironment are regulated by various families of proteases, including mainly metzincins [2] and serine proteases Their function is to cleave the proteins available in the extracellular matrix (ECM) and even to release signaling molecules from ECM and CAMs, which may play an essential role for changes in synaptic configuration. It has repeatedly been shown that the same target molecule can be recognized and processed by various proteases and the released soluble ectodomains of CAMs may interact with different ligands, leading to the generation of distinct signals

Proteolysis of Cell Adhesion Molecules

Cadherins Syndecans Immunoglobulin superfamily

Future Directions