NGL ‐3‐induced presynaptic differentiation of hippocampal neurons in an afadin‐dependent, nectin‐1‐independent manner

A hippocampal mossy fiber synapse, which is implicated in learning and memory, has a complex structure. We have previously shown using afadin‐deficient mice that afadin plays multiple roles in the structural and functional differentiations of this synapse. We investigated here using a co‐culture system with cultured hippocampal neurons and non‐neuronal COS‐7 cells expressing synaptogenic cell adhesion molecules (CAMs) whether afadin is involved in the presynaptic differentiation of hippocampal synapses. Postsynaptic CAMs NGL‐3 (alias, a Lrrc4b gene product) and neuroligin induced presynaptic differentiation by trans‐interacting with their respective presynaptic binding CAMs LAR (alias, a Ptprf gene product) and neurexin. This activity of NGL‐3, but not neuroligin, was dependent on afadin, but not the afadin‐binding presynaptic CAM nectin‐1. The afadin‐binding postsynaptic CAM nectin‐3 did not induce presynaptic differentiation. Immunofluorescence and immunoelectron microscopy analyses showed that afadin was localized mainly at puncta adherentia junctions, but partly at synaptic junctions, of the mossy fiber synapse. β‐Catenin and γ‐catenin known to bind to LAR were co‐immunoprecipitated with afadin from the lysate of mouse brain. These results suggest that afadin is involved in the NGL‐3‐LAR system‐induced presynaptic differentiation of hippocampal neurons cooperatively with β‐catenin and γ‐catenin in a nectin‐1‐independent manner...
Source: Genes to Cells - Category: Genetics & Stem Cells Authors: Tags: Original Article Source Type: research