[Frontiers in Bioscience 11, 2400-2419, September 1, 2006]

Cell adhesion molecules at the synapse

Kimberly Gerrow and Alaa El-Husseini

Department of Psychiatry, University of British Columbia, Vancouver, B.C. Canada


1. Abstract
2. Introduction to the synapse
2.1. Development of NMJ
2.2. Development of CNS synapses
3. Role of adhesion molecules in excitatory synapse development
3.1. Target Recognition and Initiation
3.2. Recruitment of Presynaptic and Postsynaptic Proteins
3.3. Maturation and Spine Morphogenesis
3.4. Elimination
4. Cell adhesion molecules implicated in inhibitory synapse development
5. Plasticity and Signaling
6. Modulation of cell adhesion molecules by scaffolding proteins
7. Synaptic imbalance in psychiatric disorders
8. Conclusions
9. References


Synapses are specialized intercellular junctions whose specificity and plasticity provide the structural and functional basis for the formation and maintenance of the complex neural network in the brain. The number, location, and type of synapses formed are well controlled, since synaptic circuits are formed in a highly reproducible way. This implies the existence of cellular and molecular properties that determine the connectivity of each neuron in the nervous system. Recent evidence has elucidated that these key features of the synapse are regulated by several families of cell-adhesion molecules (CAMs) enriched at synaptic junctions, including neuroligins, SynCAM, NCAM, L1-CAM, cadherins, protocadherins, and integrins. In this review we will discuss the various stages of synaptogenesis from the perspective of CAMs: Contact initiation, recruitment of presynaptic and postsynaptic proteins, synapse maturation/stabilization or elimination, and synaptic plasticity. We will also highlight some of the factors that regulate the function of these CAMs at the synapse, and discuss how dysfunction of these adhesive systems may contribute to several neurological disorders.