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miR-153 regulates SNAP-25, synaptic transmission, and neuronal development.

SNAP-25 is a core component of the trimeric SNARE complex mediating vesicle exocytosis during membrane addition for neuronal growth, neuropeptide/growth factor secretion, and neurotransmitter release during synaptic transmission. Here, we report a novel microRNA mechanism of SNAP-25 regulation controlling motor neuron development, neurosecretion, synaptic activity, and movement in zebrafish. Loss of miR-153 causes overexpression of SNAP-25 and consequent hyperactive movement in early zebrafish embryos. Conversely, overexpression of miR-153 causes SNAP-25 down regulation resulting in near complete paralysis, mimicking the effects of treatment with Botulinum neurotoxin. miR-153-dependent changes in synaptic activity at the neuromuscular junction are consistent with the observed movement defects. Underlying the movement defects, perturbation of miR-153 function causes dramatic developmental changes in motor neuron patterning and branching. Together, our results indicate that precise control of SNAP-25 expression by miR-153 is critically important for proper neuronal patterning as well as neurotransmission.

Pubmed ID: 23451149

Authors

  • Wei C
  • Thatcher EJ
  • Olena AF
  • Cha DJ
  • Perdigoto AL
  • Marshall AF
  • Carter BD
  • Broadie K
  • Patton JG

Journal

PloS one

Publication Data

March 1, 2013

Associated Grants

  • Agency: NEI NIH HHS, Id: EY019759
  • Agency: NINDS NIH HHS, Id: F30 NS061403
  • Agency: NIGMS NIH HHS, Id: GM 075790
  • Agency: NIGMS NIH HHS, Id: GM 54544
  • Agency: NINDS NIH HHS, Id: NS038220
  • Agency: NIMH NIH HHS, Id: R01 MH096832
  • Agency: NINDS NIH HHS, Id: R01 NS038220
  • Agency: NCRR NIH HHS, Id: RR12546
  • Agency: NIGMS NIH HHS, Id: T32 GM07347
  • Agency: NIGMS NIH HHS, Id: T32 GM08556
  • Agency: NICHD NIH HHS, Id: T32 HD007502

Mesh Terms

  • Animals
  • Base Sequence
  • Exocytosis
  • Green Fluorescent Proteins
  • MicroRNAs
  • Motor Neurons
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Synaptic Transmission
  • Synaptosomal-Associated Protein 25
  • Zebrafish