Cadherins Interact With Synaptic Organizers to Promote Synaptic Differentiation.

Frontiers in Molecular Neuroscience
Masahito YamagataJoshua R Sanes

Abstract

Classical cadherins, a set of ~20 related recognition and signaling molecules, have been implicated in many aspects of neural development, including the formation and remodeling of synapses. Mechanisms underlying some of these steps have been studied by expressing N-cadherin (cdh2), a Type 1 cadherin, in heterologous cells, but analysis is complicated because widely used lines express cdh2 endogenously. We used CRISPR-mediated gene editing to generate a Human embryonic kidney (HEK)293 variant lacking Cdh2, then compared the behavior of rodent cortical and hippocampal neurons co-cultured with parental, cdh2 mutant and cdh2-rescued 293 lines. The comparison demonstrated that Cdh2 promotes neurite branching and that it is required for three synaptic organizers, neurologin1 (NLGL1), leucine-rich repeat transmembrane protein 2 (LRRtm2), and Cell Adhesion Molecule 1 (Cadm1/SynCAM) to stimulate presynaptic differentiation, assayed by clustering of synaptic vesicles at sites of neurite-293 cell contact. Similarly, Cdh2 is required for a presynaptic organizing molecule, Neurexin1β, to promote postsynaptic differentiation in dendrites. We also show that another Type I cadherin, Cdh4, and a Type II cadherin, Cdh6, can substitute for Cdh2 ...Continue Reading

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Citations

Jan 17, 2020·ELife·Alicia N VagnozziPolyxeni Philippidou
May 20, 2020·Scientific Reports·Shahzad AhmadCornelia M van Duijn
Nov 30, 2019·Frontiers in Molecular Neuroscience·Sushma Dagar, Kurt Gottmann
Dec 16, 2020·The Journal of Comparative Neurology·Rio IkutaMami Kurumata-Shigeto
May 4, 2020·Cell·Joshua R Sanes, S Lawrence Zipursky

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