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.
Copyright © 2010 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Action Potentials / genetics
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Action Potentials / physiology
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Animals
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Animals, Genetically Modified
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Calcium / metabolism
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Calcium Channels, N-Type / genetics
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Calcium Channels, N-Type / metabolism
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Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
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Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
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Cell Adhesion Molecules, Neuronal / metabolism
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Drosophila
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism
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Electric Stimulation / methods
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Embryo, Nonmammalian
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Gene Expression Regulation, Developmental / genetics
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Genetic Testing
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Larva
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Motor Neurons / cytology
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Motor Neurons / physiology
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Muscles / metabolism
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Muscles / physiology
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Mutation / genetics
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Neuromuscular Junction* / cytology
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Neuromuscular Junction* / growth & development
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Neuromuscular Junction* / metabolism
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Presynaptic Terminals / physiology*
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism
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Semaphorins / genetics
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Semaphorins / metabolism*
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Signal Transduction / genetics
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Signal Transduction / physiology*
Substances
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Calcium Channels, N-Type
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Cell Adhesion Molecules, Neuronal
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Drosophila Proteins
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Nerve Tissue Proteins
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Receptors, Cell Surface
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Semaphorins
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fasciclin II
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plexB protein, Drosophila
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voltage-dependent calcium channel (P-Q type)
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium