AUTHOR=Regus-Leidig Hanna , Fuchs Michaela , Löhner Martina , Leist Sarah R. , Leal-Ortiz Sergio , Chiodo Vince A. , Hauswirth William W. , Garner Craig C. , Brandstätter Johann H. TITLE=In vivo knockdown of Piccolino disrupts presynaptic ribbon morphology in mouse photoreceptor synapses JOURNAL=Frontiers in Cellular Neuroscience VOLUME=8 YEAR=2014 URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2014.00259 DOI=10.3389/fncel.2014.00259 ISSN=1662-5102 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.