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NGL ‐3‐induced presynaptic differentiation of hippocampal neurons in an afadin‐dependent, nectin‐1‐independent manner
Author(s) -
Maruo Tomohiko,
Mandai Kenji,
Miyata Muneaki,
Sakakibara Shotaro,
Wang Shujie,
Sai Kousyoku,
Itoh Yu,
Kaito Aika,
Fujiwara Takeshi,
Mizoguchi Akira,
Takai Yoshimi
Publication year - 2017
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12510
Subject(s) - biology , postsynaptic potential , hippocampal formation , nectin , microbiology and biotechnology , synapse , mossy fiber (hippocampus) , neuroscience , cell adhesion , dentate gyrus , cell , receptor , biochemistry
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 ( CAM s) whether afadin is involved in the presynaptic differentiation of hippocampal synapses. Postsynaptic CAM s NGL ‐3 (alias, a Lrrc4b gene product) and neuroligin induced presynaptic differentiation by trans ‐interacting with their respective presynaptic binding CAM s 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.