title: Absence of functional active zone protein Bassoon affects assembly and transport of ribbon precursors during early steps of photoreceptor synaptogenesis.
abstract: The retinal photoreceptor ribbon synapse is a structurally and functionally unique type of chemical synapse, specialized for tonic release of neurotransmitter in the dark. It is characterized by the presynaptic ribbon, an electron-dense organelle at the active zone, which is covered by hundreds of synaptic vesicles. Recently we showed that photoreceptor ribbon complexes are assembled from non-membranous, spherical densities--the precursor spheres--during the first two postnatal weeks of photoreceptor synaptogenesis. A core component of the precursor spheres and a key player in attaching the ribbon to the active zone is the presynaptic cytomatrix protein Bassoon. In this study, we examined in a comprehensive light and electron microscopic analysis whether Bassoon plays a role in the formation of the precursor spheres using Bassoon mutant mice lacking functional Bassoon. We report that developing Bassoon mutant photoreceptors contain fewer and smaller precursor spheres and that transport of precursor spheres to nascent synapses is delayed compared to wild-type controls. Moreover, western blot analyses of homogenates from postnatal day 0 (P0) to P14 Bassoon mutant retinae exhibit lower RIBEYE and Piccolo protein levels compared to the wild type, indicating elevated protein degradation in the absence of Bassoon. Our findings reveal a novel function of Bassoon in the early formation and delivery of precursor spheres to nascent ribbon synaptic sites in addition to its known role in ribbon anchoring during later stages of photoreceptor ribbon synaptogenesis.
authors.affiliation: Department of Biology, Animal Physiology, University of Erlangen-Nuremberg, Staudtstr. 5, 91058 Erlangen, Germany.
authors.forename: Hanna
authors.initials: H
authors.lastname: Regus-Leidig
authors.forename: Susanne
authors.initials: S
authors.lastname: tom Dieck
authors.forename: Johann Helmut
authors.initials: JH
authors.lastname: Brandstätter
mesh_terms: D000818:Animals; D015153:Blotting, Western; D007834:Lasers; D051379:Mice; D042282:Microdissection; D046529:Microscopy, Electron, Transmission; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010786:Photoreceptor Cells / Q000378:metabolism* / Q000648:ultrastructure*; D021381:Protein Transport; D012160:Retina / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure*
chemical_list: C498441:Bsn protein, mouse; D009419:Nerve Tissue Proteins