title: Aberrant function and structure of retinal ribbon synapses in the absence of complexin 3 and complexin 4.
abstract: Complexins regulate the speed and Ca(2+) sensitivity of SNARE-mediated synaptic vesicle fusion at conventional synapses. Two of the vertebrate complexins, Cplx3 and Cplx4, are specifically localized to retinal ribbon synapses. To test whether Cplx3 and Cplx4 contribute to the highly efficient transmitter release at ribbon synapses, we studied retina function and structure in Cplx3 and Cplx4 single- and double-knockout mice. Electroretinographic recordings from single and double mutants revealed a cooperative perturbing effect of Cplx3 and Cplx4 deletion on the b-wave amplitude, whereas most other detected effects in both plexiform synaptic layers were additive. Light and electron microscopic analyses uncovered a disorganized outer plexiform layer in the retinae of mice lacking Cplx3 and Cplx4, with a significant proportion of photoreceptor terminals containing spherical free-floating ribbons. These structural and functional aberrations were accompanied by behavioural deficits indicative of a vision deficit. Our results show that Cplx3 and Cplx4 are essential regulators of transmitter release at retinal ribbon synapses. Their loss leads to aberrant adjustment and fine-tuning of transmitter release at the photoreceptor ribbon synapse, alterations in transmission at bipolar cell terminals, changes in the temporal structure of synaptic processing in the inner plexiform layer of the retina and perturbed vision.
authors.affiliation: Department of Molecular Neurobiology and Center for the Molecular Physiology of the Brain, Max Planck Institute of Experimental Medicine, D-37075 Göttingen, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Reim
authors.forename: Hanna
authors.initials: H
authors.lastname: Regus-Leidig
authors.forename: Josef
authors.initials: J
authors.lastname: Ammermüller
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Kordi
authors.forename: Konstantin
authors.initials: K
authors.lastname: Radyushkin
authors.forename: Hannelore
authors.initials: H
authors.lastname: Ehrenreich
authors.forename: Johann Helmut
authors.initials: JH
authors.lastname: Brandstätter
authors.forename: Nils
authors.initials: N
authors.lastname: Brose
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000429:Alcohol Oxidoreductases; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D056970:Co-Repressor Proteins; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010786:Photoreceptor Cells / Q000378:metabolism / Q000648:ultrastructure; D012160:Retina / Q000378:metabolism / Q000648:ultrastructure; D050600:SNARE Proteins / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology; D014786:Vision Disorders / Q000503:physiopathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; C498441:Bsn protein, mouse; D056970:Co-Repressor Proteins; C529624:Cplx3 protein, mouse; C543115:Cplx4 protein, mouse; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; C498631:Pclo protein, mouse; D010750:Phosphoproteins; D050600:SNARE Proteins; D000429:Alcohol Oxidoreductases; C111341:Ctbp2 protein, mouse