Synapsin III acts downstream of semaphorin 3A/CDK5 signaling to regulate radial migration and orientation of pyramidal neurons in vivo

Cell Rep. 2015 Apr 14;11(2):234-48. doi: 10.1016/j.celrep.2015.03.022. Epub 2015 Apr 2.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • C-Reactive Protein / genetics
  • COS Cells
  • Cell Movement / genetics
  • Cerebral Cortex / growth & development*
  • Chlorocebus aethiops
  • Cyclin-Dependent Kinase 5 / biosynthesis
  • Cyclin-Dependent Kinase 5 / genetics*
  • Dendrites / genetics
  • Dendrites / metabolism
  • Gene Expression Regulation, Developmental
  • Mice
  • Nerve Tissue Proteins / genetics
  • Phosphorylation
  • Primary Cell Culture
  • Pyramidal Cells / cytology
  • Pyramidal Cells / metabolism
  • Rats
  • Semaphorin-3A / biosynthesis*
  • Semaphorin-3A / genetics
  • Signal Transduction
  • Synapsins / biosynthesis
  • Synapsins / genetics*


  • Nerve Tissue Proteins
  • Semaphorin-3A
  • Synapsins
  • neuronal pentraxin
  • C-Reactive Protein
  • Cyclin-Dependent Kinase 5
  • Cdk5 protein, rat