Presynaptic activity and CaMKII modulate retrograde semaphorin signaling and synaptic refinement

Neuron. 2010 Oct 6;68(1):32-44. doi: 10.1016/j.neuron.2010.09.005.

Abstract

Establishing synaptic connections often involves the activity-dependent withdrawal of off-target contacts. We describe an in vivo role for temporally patterned electrical activity, voltage-gated calcium channels, and CaMKII in modulating the response of Drosophila motoneurons to the chemorepellent Sema-2a during synaptic refinement. Mutations affecting the Sema-2a ligand, the plexin B receptor (plexB), the voltage-gated Ca(v)2.1 calcium channel (cac), or the voltage-gated Na(v)1 sodium channel (mle(nap-ts);tipE) each result in ectopic neuromuscular contacts. Sema-2a interacts genetically with both of the channel mutations. The cac phenotype is enhanced by the Sema-2a mutation and is suppressed by either plexB overexpression or patterned, low-frequency (0.01 Hz) bouts of electrical activity in the embryo. The calcium-dependent suppression of ectopic contacts also depends on the downstream activation of CaMKII. These results indicate a role for patterned electrical activity and presynaptic calcium signaling, acting through CaMKII, in modulating a retrograde signal during the refinement of synaptic connections.

Publication types

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

MeSH terms

  • Action Potentials / genetics
  • Action Potentials / physiology
  • Animals
  • Animals, Genetically Modified
  • Calcium / metabolism
  • Calcium Channels, N-Type / genetics
  • Calcium Channels, N-Type / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Drosophila
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Electric Stimulation / methods
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental / genetics
  • Genetic Testing
  • Larva
  • Motor Neurons / cytology
  • Motor Neurons / physiology
  • Muscles / metabolism
  • Muscles / physiology
  • Mutation / genetics
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neuromuscular Junction* / cytology
  • Neuromuscular Junction* / growth & development
  • Neuromuscular Junction* / metabolism
  • Presynaptic Terminals / physiology*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Semaphorins / genetics
  • Semaphorins / metabolism*
  • Signal Transduction / genetics
  • Signal Transduction / physiology*

Substances

  • Calcium Channels, N-Type
  • Cell Adhesion Molecules, Neuronal
  • Drosophila Proteins
  • Nerve Tissue Proteins
  • Receptors, Cell Surface
  • Semaphorins
  • fasciclin II
  • plexB protein, Drosophila
  • voltage-dependent calcium channel (P-Q type)
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium