PUBLICATION
N-cadherin prodomain cleavage regulates synapse formation in vivo
- Authors
- Latefi, N.S., Pedraza, L., Schohl, A., Li, Z., and Ruthazer, E.S.
- ID
- ZDB-PUB-090417-5
- 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.
Citation
Latefi, N.S., Pedraza, L., Schohl, A., Li, Z., and Ruthazer, E.S. (2009) N-cadherin prodomain cleavage regulates synapse formation in vivo. Developmental Neurobiology. 69(8):518-529.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping