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First published online April 22, 2009
doi: 10.1242/10.1242/jcs.045401
Research Article |
1 Department of Molecular Neurobiology and Center for the Molecular Physiology of the Brain, Max Planck Institute of Experimental Medicine, D-37075 Göttingen, Germany
2 Department of Biology, Animal Physiology, University of Erlangen-Nuremberg, D-91058 Erlangen, Germany
3 AG Neurobiology, Carl von Ossietzky University of Oldenburg, D-26111 Oldenburg, Germany
4 Division of Clinical Neuroscience and Center for the Molecular Physiology of the Brain, Max Planck Institute of Experimental Medicine, D-37075 Göttingen, Germany
* Authors for correspondence (e-mails: jbrandst{at}biologie.uni-erlangen.de; brose{at}em.mpg.de)
Accepted 10 January 2009
Complexins regulate the speed and Ca2+ 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.
Key words: Complexin, Exocytosis, SNARE, Ribbon synapse, ERG, Photoreceptors, Bipolar cells
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