Temporal and spatial localization of nectin-1 and l-afadin during synaptogenesis in hippocampal neurons.

Nectins are cell adhesion molecules that, together with the intracellular binding partner afadin, mediate adhesion and signaling at a variety of intercellular junctions. In this work we studied the distribution of nectin-1 and afadin during hippocampal synapse formation using cultured primary hippocampal neurons. Nectin-1 and afadin cluster at developing synapses between hippocampal neurons. These nectin-afadin clusters uniformly colocalize with N-cadherin-catenin pairs, suggesting that formation of developing synapses involves participation of both bimolecular systems. Nectin-1 is initially expressed at excitatory and inhibitory synapses but is progressively lost at inhibitory synapses during their maturation. Treatment of neurons with actin depolymerizing agents disrupts the synaptically localized nectin-1 and afadin cluster at an early stage and elicits nectin-1 ectodomain shedding. These data indicate that the synaptic localization of nectin-1 and l-afadin are F-actin-dependent and that the shedding of nectin-1 is a mechanism contributing to synaptic plasticity.