title: In vivo knockdown of Piccolino disrupts presynaptic ribbon morphology in mouse photoreceptor synapses.
abstract: Piccolo is the largest known cytomatrix protein at active zones of chemical synapses. A growing number of studies on conventional chemical synapses assign Piccolo a role in the recruitment and integration of molecules relevant for both endo- and exocytosis of synaptic vesicles, the dynamic assembly of presynaptic F-actin, as well as the proteostasis of presynaptic proteins, yet a direct function in the structural organization of the active zone has not been uncovered in part due to the expression of multiple alternatively spliced isoforms. We recently identified Piccolino, a Piccolo splice variant specifically expressed in sensory ribbon synapses of the eye and ear. Here we down regulated Piccolino in vivo via an adeno-associated virus-based RNA interference approach and explored the impact on the presynaptic structure of mouse photoreceptor ribbon synapses. Detailed immunocytochemical light and electron microscopical analysis of Piccolino knockdown in photoreceptors revealed a hitherto undescribed photoreceptor ribbon synaptic phenotype with striking morphological changes of synaptic ribbon ultrastructure.
authors.affiliation: Department of Biology, Animal Physiology, Friedrich-Alexander-University of Erlangen-Nuremberg Erlangen, Germany.
authors.forename: Hanna
authors.initials: H
authors.lastname: Regus-Leidig
authors.affiliation: Department of Biology, Animal Physiology, Friedrich-Alexander-University of Erlangen-Nuremberg Erlangen, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Fuchs
authors.affiliation: Department of Biology, Animal Physiology, Friedrich-Alexander-University of Erlangen-Nuremberg Erlangen, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Löhner
authors.affiliation: Department of Biology, Animal Physiology, Friedrich-Alexander-University of Erlangen-Nuremberg Erlangen, Germany ; Department of Infection Genetics, Helmholtz Centre for Infection Research Braunschweig, Germany.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Leist
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University Palo Alto, CA, USA.
authors.forename: Sergio
authors.initials: S
authors.lastname: Leal-Ortiz
authors.affiliation: Department of Ophthalmology, College of Medicine, University of Florida Gainesville, FL, USA.
authors.forename: Vince A
authors.initials: VA
authors.lastname: Chiodo
authors.affiliation: Department of Ophthalmology, College of Medicine, University of Florida Gainesville, FL, USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Hauswirth
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University Palo Alto, CA, USA ; Deutsches Zentrum für Neurodegenerative Erkrankungen Charité, Berlin, Germany.
authors.forename: Craig C
authors.initials: CC
authors.lastname: Garner
authors.affiliation: Department of Biology, Animal Physiology, Friedrich-Alexander-University of Erlangen-Nuremberg Erlangen, Germany.
authors.forename: Johann H
authors.initials: JH
authors.lastname: Brandstätter
keywords: Aczonin; Piccolino; Piccolo; RIBEYE; active zone; retina; ribbon synapse