title: Shedding of neurexin 3β ectodomain by ADAM10 releases a soluble fragment that affects the development of newborn neurons.
abstract: Neurexins are transmembrane synaptic cell adhesion molecules involved in the development and maturation of neuronal synapses. In the present study, we report that Nrxn3β is processed by the metalloproteases ADAM10, ADAM17, and by the intramembrane-cleaving protease γ-secretase, producing secreted neurexin3β (sNrxn3β) and a single intracellular domain (Nrxn3β-ICD). We further completed the full characterization of the sites at which Nrxn3β is processed by these proteases. Supporting the physiological relevance of the Nrxn3β processing, we demonstrate in vivo a significant effect of the secreted shedding product sNrxn3β on the morphological development of adult newborn neurons in the mouse hippocampus. We show that sNrxn3β produced by the cells of the dentate gyrus increases the spine density of newborn neurons whereas sNrxn3β produced by the newborn neuron itself affects the number of its mossy fiber terminal extensions. These results support a pivotal role of sNrxn3β in plasticity and network remodeling during neuronal development.
authors.affiliation: Brain Mind Institute and School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH1015 Lausanne, Switzerland.
authors.forename: Erika
authors.initials: E
authors.lastname: Borcel
authors.affiliation: Brain Mind Institute and School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH1015 Lausanne, Switzerland.
authors.forename: Magda
authors.initials: M
authors.lastname: Palczynska
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne (UNIL), CH1015 Lausanne, Switzerland.
authors.forename: Marine
authors.initials: M
authors.lastname: Krzisch
authors.affiliation: Brain Mind Institute and School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH1015 Lausanne, Switzerland.
authors.forename: Mitko
authors.initials: M
authors.lastname: Dimitrov
authors.affiliation: Brain Mind Institute and School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH1015 Lausanne, Switzerland.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Ulrich
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne (UNIL), CH1015 Lausanne, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Toni
authors.affiliation: Brain Mind Institute and School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH1015 Lausanne, Switzerland.|Foundation Eclosion, CH1228 Plan-Les-Ouates &Campus Biotech Innovation Park, CH1202 Geneva, Switzerland.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Fraering
mesh_terms: D000072197:ADAM10 Protein / Q000378:metabolism*; D000072198:ADAM17 Protein / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D006624:Hippocampus / Q000166:cytology*; D008565:Membrane Proteins / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D059748:Proteolysis
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C583456:neurexin 3, mouse; D053829:Amyloid Precursor Protein Secretases; D000072197:ADAM10 Protein; C491234:Adam10 protein, mouse; D000072198:ADAM17 Protein; C000606463:Adam17 protein, mouse