Abstract
Immunoglobulin superfamily adhesion molecules are among the most abundant proteins in vertebrate and invertebrate nervous systems. Prominent family members are the neural cell adhesion molecules NCAM and L1, which were the first to be shown to be essential not only in development but also in synaptic function and as key regulators of synapse formation, synaptic activity, plasticity, and synaptic vesicle recycling at distinct developmental and activity stages. In addition to interacting with each other, adhesion molecules interact with ion channels and cytokine and neurotransmitter receptors. Mutations in their genes are linked to neurological disorders associated with abnormal development and synaptic functioning. This review presents an overview of recent studies on these molecules and their crucial impact on neurological disorders.
Experimentally induced changes in expression of NCAM and L1 family members affect synaptic plasticity, learning and memory, and behavior. These effects are exacerbated by stress and aging.
NCAM and L1 family members regulate the numbers and maturation of excitatory and inhibitory synapses, and changes in the levels of these cell adhesion molecules are required for the activity-dependent stabilization and destabilization of synapses.
NCAM and L1 family members regulate synaptic activity by associating with and recruiting neurotransmission-related molecules to synapses, regulating synaptic vesicle exo- and endocytosis, and inducing intracellular signaling cascades.
Gene alterations, as well as changes in the expression levels of their proteins and in the extent of post-translational modification of NCAM and L1 family members, are associated with human brain disorders linked to abnormal synaptic function.