TY - JOUR

T1 - Munc13-independent vesicle priming at mouse photoreceptor ribbon synapses

AU - Cooper, Benjamin

AU - Hemmerlein, Maike

AU - Ammermüller, Josef

AU - Imig, Cordelia

AU - Reim, Kerstin

AU - Lipstein, Noa

AU - Kalla, Stefan

AU - Kawabe, Hiroshi

AU - Brose, Nils

AU - Brandstätter, Johann Helmut

AU - Varoqueaux, Frédérique

PY - 2012/6/6

Y1 - 2012/6/6

N2 - 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.

AB - 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.

KW - Amacrine Cells/physiology

KW - Animals

KW - Cloning, Molecular

KW - DNA, Complementary/biosynthesis

KW - Electroretinography

KW - Exocytosis/genetics

KW - Fluorescent Antibody Technique

KW - Immunohistochemistry

KW - Intracellular Signaling Peptides and Proteins/genetics

KW - Isomerism

KW - Mice

KW - Mice, Knockout

KW - Microscopy, Electron

KW - Nerve Tissue Proteins/genetics

KW - RNA/biosynthesis

KW - Retina/cytology

KW - Synapses/physiology

KW - Synaptic Vesicles/drug effects

KW - Transcription, Genetic

U2 - 10.1523/JNEUROSCI.4240-11.2012

DO - 10.1523/JNEUROSCI.4240-11.2012

M3 - Journal article

C2 - 22674279

VL - 32

SP - 8040

EP - 8052

JO - The Journal of neuroscience : the official journal of the Society for Neuroscience

JF - The Journal of neuroscience : the official journal of the Society for Neuroscience

SN - 0270-6474

IS - 23

ER -