title: Synapsin III acts downstream of semaphorin 3A/CDK5 signaling to regulate radial migration and orientation of pyramidal neurons in vivo.
abstract: Synapsin III (SynIII) is a phosphoprotein that is highly expressed at early stages of neuronal development. Whereas in vitro evidence suggests a role for SynIII in neuronal differentiation, in vivo evidence is lacking. Here, we demonstrate that in vivo downregulation of SynIII expression affects neuronal migration and orientation. By contrast, SynIII overexpression affects neuronal migration, but not orientation. We identify a cyclin-dependent kinase-5 (CDK5) phosphorylation site on SynIII and use phosphomutant rescue experiments to demonstrate its role in SynIII function. Finally, we show that SynIII phosphorylation at the CDK5 site is induced by activation of the semaphorin-3A (Sema3A) pathway, which is implicated in migration and orientation of cortical pyramidal neurons (PNs) and is known to activate CDK5. Thus, fine-tuning of SynIII expression and phosphorylation by CDK5 activation through Sema3A activity is essential for proper neuronal migration and orientation.
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genoa 16163, Italy; Department of Experimental Medicine, University of Genoa, Genoa 16132, Italy.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Perlini
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genoa 16163, Italy.
authors.forename: Joanna
authors.initials: J
authors.lastname: Szczurkowska
authors.affiliation: Department of Biology, University of Vermont, Burlington, VT 05405-0086, USA.
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Ballif
authors.affiliation: Department of Experimental Medicine, University of Genoa, Genoa 16132, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Piccini
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genoa 16163, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Sacchetti
authors.affiliation: Department of Experimental Medicine, University of Genoa, Genoa 16132, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Giovedì
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genoa 16163, Italy; Department of Experimental Medicine, University of Genoa, Genoa 16132, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Benfenati
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genoa 16163, Italy. Electronic address: laura.cancedda@iit.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Cancedda
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000235:genetics; D019556:COS Cells; D002465:Cell Movement / Q000235:genetics; D002540:Cerebral Cortex / Q000254:growth & development*; D002522:Chlorocebus aethiops; D051360:Cyclin-Dependent Kinase 5 / Q000096:biosynthesis / Q000235:genetics*; D003712:Dendrites / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics; D010766:Phosphorylation; D061251:Primary Cell Culture; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism; D051381:Rats; D040121:Semaphorin-3A / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D016704:Synapsins / Q000096:biosynthesis / Q000235:genetics*; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D051360:Cyclin-Dependent Kinase 5; D009419:Nerve Tissue Proteins; D040121:Semaphorin-3A; D016704:Synapsins; D000099153:Pentraxins; C495907:Cdk5 protein, rat
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