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ZFIN ID: ZDB-PUB-090417-5
N-cadherin prodomain cleavage regulates synapse formation in vivo
Latefi, N.S., Pedraza, L., Schohl, A., Li, Z., and Ruthazer, E.S.
Date: 2009
Source: Developmental Neurobiology   69(8): 518-529 (Journal)
Registered Authors:
Keywords: cadherin, zebrafish, Rohon-Beard, synaptogenesis, prodomain
MeSH Terms:
  • Animals
  • Axons/metabolism
  • Axons/ultrastructure
  • Brain/cytology
  • Brain/embryology*
  • Brain/metabolism*
  • Cadherins/chemistry
  • Cadherins/genetics
  • Cadherins/metabolism*
  • Cell Differentiation/physiology
  • Cells, Cultured
  • Green Fluorescent Proteins/genetics
  • Green Fluorescent Proteins/metabolism
  • Kinetics
  • Mutation/genetics
  • Neural Pathways/embryology
  • Neural Pathways/metabolism
  • Neural Pathways/ultrastructure
  • Protein Structure, Tertiary/physiology
  • Recombinant Fusion Proteins/genetics
  • Recombinant Fusion Proteins/metabolism
  • Synapses/metabolism*
  • Synapses/ultrastructure
  • Synaptic Membranes/metabolism
  • Synaptic Membranes/ultrastructure
  • Zebrafish/anatomy & histology
  • Zebrafish/embryology*
  • Zebrafish/metabolism*
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 19365814 Full text @ Dev. Neurobiol.
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.