Munc13-independent vesicle priming at mouse photoreceptor ribbon synapses

J Neurosci. 2012 Jun 6;32(23):8040-52. doi: 10.1523/JNEUROSCI.4240-11.2012.

Abstract

Munc13 proteins are essential regulators of exocytosis. In hippocampal glutamatergic neurons, the genetic deletion of Munc13s results in the complete loss of primed synaptic vesicles (SVs) in direct contact with the presynaptic active zone membrane, and in a total block of neurotransmitter release. Similarly drastic consequences of Munc13 loss are detectable in hippocampal and striatal GABAergic neurons. We show here that, in the adult mouse retina, the two Munc13-2 splice variants bMunc13-2 and ubMunc13-2 are selectively localized to conventional and ribbon synapses, respectively, and that ubMunc13-2 is the only Munc13 isoform in mature photoreceptor ribbon synapses. Strikingly, the genetic deletion of ubMunc13-2 has little effect on synaptic signaling by photoreceptor ribbon synapses and does not prevent membrane attachment of synaptic vesicles at the photoreceptor ribbon synaptic site. Thus, photoreceptor ribbon synapses and conventional synapses differ fundamentally with regard to their dependence on SV priming proteins of the Munc13 family. Their function is only moderately affected by Munc13 loss, which leads to slight perturbations of signal integration in the retina.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amacrine Cells / physiology
  • Animals
  • Cloning, Molecular
  • DNA, Complementary / biosynthesis
  • DNA, Complementary / genetics
  • Electroretinography
  • Exocytosis / genetics
  • Exocytosis / physiology
  • Fluorescent Antibody Technique
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Isomerism
  • Mice
  • Mice, Knockout
  • Microscopy, Electron
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • RNA / biosynthesis
  • RNA / genetics
  • Retina / cytology
  • Retina / physiology
  • Retina / ultrastructure
  • Synapses / physiology*
  • Synapses / ultrastructure
  • Synaptic Vesicles / drug effects
  • Synaptic Vesicles / physiology*
  • Synaptic Vesicles / ultrastructure
  • Transcription, Genetic

Substances

  • DNA, Complementary
  • Intracellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Unc13b protein, mouse
  • RNA