N-Cadherin Prodomain Processing Regulates Synaptogenesis

• DOI: 10.1523/jneurosci.0916-12.2012
• Publication Date: 2012-05-02T16:53:49Z
• Authors: Analía Reinés; Louis-Philippe Be...; Robyn McAdam; Wiam Belkaid; Weisong Shan; Alexander W. Koch; Philippe Séguéla; David R. Colman; Ajit S. Dhaunchak
• Keywords: Synaptogenesis; Cleavage (geology)

Classical cadherins, which are adhesion molecules functioning at the CNS synapse, synthesized as adhesively inactive precursor proteins in endoplasmic reticulum (ER). Signal sequence and prodomain cleavage ER Golgi apparatus, respectively, activates their adhesive properties. Here, we provide first evidence for sorting of nonadhesive N-cadherin (ProN) to neuronal surface, where it coexists with competent mature (N-cad), generating a spectrum strengths. In cultured hippocampal neurons, high ProN/N-cad ratio downregulates synapse formation. Neurons expressing genetically engineered uncleavable ProN make markedly fewer synapses. The number can be rescued normality by depleting surface levels through an exogenous protease. Finally, processing is developmentally regulated rat hippocampus. We conclude that not N-cad alone critical regulation during synaptogenesis.