Integrins in synapse regulation

Integrins are major cell surface receptors for the extracellular matrix (ECM). Intracellularly, integrins link to the actin cytoskeleton and signalling systems and thus function as mechanochemical signal transducers between the extracellular environment and the cell.Integrins are heterodimers of α- and β-subunits, and many integrin subtypes are expressed in the brain. During development, integrins have multifaceted roles in differentiation and maintenance of neural stem cells, axon outgrowth and dendrite arborization, in concert with signalling involving the ECM, growth factor receptors and adhesion proteins.Synaptic integrins detect dynamic changes in the extracellular synaptic milieu and coordinate synapse structure and function. Integrins regulate synapse formation and maturation, in concert with glial signals, regulate postsynaptic strength by controlling neurotransmitter receptor dynamics and alter dendritic spine shape by triggering actin remodelling.Different integrin subtypes participate in distinct forms of synaptic plasticity. Presumably, the differences reflect the differences in their biophysical properties, molecular interactors and signalling systems to which they are linked under specific cellular contexts.The differential expression pattern of the integrin subtypes may also provide the basis for the subtle differences in behavioural phenotypes that are associated with mice deficient in particular subtypes of integrin. In the hippocampus, β1-containing integrins are required for working memory, whereas β3-containing integrins seem to be involved in emotional behaviours.Much remains to be clarified about the basic properties of synaptic integrins, including the detailed cellular and subcellular expression of each of the subtypes in different brain regions and in circuits underlying specific behaviours, the native extracellular ligands of synaptic integrins and their dynamic regulation modulated by ECM remodelling, and the interactions of synaptic integrins with other binding partners within and outside synapses.