Munc13-independent vesicle priming at mouse photoreceptor ribbon synapses.
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.
Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, D-37075 Göttingen, Germany.
Benjamin
B
Cooper
Maike
M
Hemmerlein
Josef
J
Ammermüller
Cordelia
C
Imig
Kerstin
K
Reim
Noa
N
Lipstein
Stefan
S
Kalla
Hiroshi
H
Kawabe
Nils
N
Brose
Johann Helmut
JH
Brandstätter
Frédérique
F
Varoqueaux
D025042:Amacrine Cells / Q000502:physiology; D000818:Animals; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004596:Electroretinography; D005089:Exocytosis / Q000235:genetics / Q000502:physiology; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D007536:Isomerism; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D012160:Retina / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D013572:Synaptic Vesicles / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D014158:Transcription, Genetic
D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C485549:Unc13b protein, mouse; D012313:RNA