N-cadherin prodomain processing regulates synaptogenesis.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Analía ReinésAjit S Dhaunchak

Abstract

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

Citations

Apr 29, 2015·Cell Adhesion & Migration·Eunju SeongJyothi Arikkath
Feb 15, 2014·Cell Adhesion & Migration·Alicia F PaulsonPasquale Manzerra
Aug 22, 2014·The Journal of Biological Chemistry·Fu-Zon ChungKojo S J Elenitoba-Johnson
Apr 8, 2015·Acta Crystallographica. Section F, Structural Biology Communications·Andrea Dalle VedoveEmilio Parisini
Sep 29, 2018·Proceedings of the National Academy of Sciences of the United States of America·Zachi HornMary E Hatten
Jun 20, 2019·Frontiers in Aging Neuroscience·Sandra Cristina ZárateAnalía Gabriela Reinés
Jan 26, 2017·Frontiers in Molecular Neuroscience·Kévin BarangerSantiago Rivera
Mar 1, 2015·The Journal of Biological Chemistry·Li YuanJyothi Arikkath
Nov 22, 2017·The Journal of Comparative Neurology·Anne Schaarschuch, Nicole Hertel
Aug 24, 2021·Frontiers in Pharmacology·Marianela Evelyn TraettaAnalía Reinés
Jun 10, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Seema PatelNadeem Akhtar

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