During embryonic development, neurons send out axons and dendrites. And though dendrites bump into other dendrites, only connections between axons and dendrites mature into synapses.
Cadherin and catenin proteins are found on both sides of a neuronal synapse and are required for synapse formation but do not appear to control the selective attachment between axons and dendrites. Members of the nectin subfamily of immunoglobulin proteins, however, are distributed asymmetrically at mature synapses with nectin-1 (N1) on the axonal side and nectin-3 (N3) on the dendritic side.
Looking at hippocampal neurons in culture, Togashi et al. found that N1 expression was restricted to axonal projections and the localization was dependent on the protein's cytoplasmic domain. N3 was expressed throughout the cell but was more abundant in dendrites.
Disruption of these patterns by overexpression of N1, which drove N1 into dendrites, led to inappropriate dendro-dentritic contact. N1–N3 complexes were formed at these abnormal contacts. Additionally, linking the N3 cytoplasmic domain to the N1 ectodomain led to aberrant junctions.
After the nectin proteins formed heterophilic connections, cadherin and catenin proteins accumulated at the nascent synapse and formed homophilic connections, allowing maturation of the junction. Togashi et al. hypothesize that such interplay of heterophilic and homophilic adhesion molecules gives cells the variety of contacts they need to sort properly.