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N‐cadherin prodomain cleavage regulates synapse formation in vivo
Author(s) -
Latefi Nazlie S.,
Pedraza Liliana,
Schohl Anne,
Li Ziwei,
Ruthazer Edward S.
Publication year - 2009
Publication title -
developmental neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.716
H-Index - 129
eISSN - 1932-846X
pISSN - 1932-8451
DOI - 10.1002/dneu.20718
Subject(s) - synaptogenesis , cadherin , zebrafish , microbiology and biotechnology , biology , synapse , cleavage (geology) , postsynaptic potential , green fluorescent protein , neuroscience , cell , gene , genetics , paleontology , receptor , fracture (geology)
Cadherins are initially synthesized bearing a prodomain that is thought to limit adhesion during early stages of biosynthesis. Functional cadherins lack this prodomain, raising the intriguing possibility that cells may utilize prodomain cleavage as a means to temporally or spatially regulate adhesion after delivery of cadherin to the cell surface. In support of this idea, immunostaining for the prodomain of zebrafish N‐cadherin revealed enriched labeling at neuronal surfaces at the soma and along axonal processes. To determine whether post‐translational cleavage of the prodomain affects synapse formation, we imaged Rohon‐Beard cells in zebrafish embryos expressing GFP‐tagged wild‐type N‐cadherin (NCAD‐GFP) or a GFP‐tagged N‐cadherin mutant expressing an uncleavable prodomain (PRON‐GFP) rendering it nonadhesive. NCAD‐GFP accumulated at synaptic microdomains in a developmentally regulated manner, and its overexpression transiently accelerated synapse formation. PRON‐GFP was much more diffusely distributed along the axon and its overexpression delayed synapse formation. Our results support the notion that N‐cadherin serves to stabilize pre‐ to postsynaptic contacts early in synapse development and suggests that regulated cleavage of the N‐cadherin prodomain may be a mechanism by which the kinetics of synaptogenesis are regulated. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2009