The ZebrafishnrcMutant Reveals a Role for the Polyphosphoinositide Phosphatase Synaptojanin 1 in Cone Photoreceptor Ribbon Anchoring

Abstract

Visual, vestibular, and auditory neurons rely on ribbon synapses for rapid continuous release and recycling of synaptic vesicles. Molecular mechanisms responsible for the properties of ribbon synapses are mostly unknown. The zebrafish vision mutant nrc has unanchored ribbons and abnormal synaptic transmission at cone photoreceptor synapses. We used positional cloning to identify the nrc mutation as a premature stop codon in the synaptojanin1 (synj1) gene. Synaptojanin 1 (Synj1) is undetectable in nrc extracts, and biochemical activities associated with it are reduced. Furthermore, morpholinos directed against synj1 phenocopy the nrc mutation. Synj1 is a polyphosphoinositide phosphatase important at conventional synapses for clathrin-mediated endocytosis and actin cytoskeletal rearrangement. In the nrc cone photoreceptor pedicle, not only are ribbons unanchored, but synaptic vesicles are reduced in number, abnormally distributed, and interspersed within a dense cytoskeletal matrix. Our findings reveal a new role for Synj1 and link phosphoinositide metabolism to ribbon architecture and function at the cone photoreceptor synapse.

Pineal-specific agouti protein regulates teleost background adaptation

“…In contrast, the blind nrc mutant exhibits apparently normal pineal photoreceptors, as examined by electron microscopy (30). nrc encodes synaptojanin1, a polyphosphoinositide phosphatase involved in clathrin-mediated endocytosis that is required for proper structure and function of cone photoreceptor synapses (40). Thus, our data collected from these animals clearly show that visual phototransduction using cone photoreceptors is not required for melanosome aggregation, expression of agrp2, or up-regulation of pmch and pmchl expression by exposure to a white background.…”

Analysis and functional evaluation of the hair-cell transcriptome

“…Disruption of the corresponding gene in mice produces deficits in vesicle uncoating and fission during synaptic-vesicle recycling at conventional synapses (34). Mutation of synaptojanin 1 in zebrafish yields the no optokinetic response c (nrc) phenotype characterized by unanchored ribbons and abnormal synaptic transmission in cone photoreceptors (35). Some nrc mutants lack the acoustic startle response, an assay used to identify deaf zebrafish (our unpublished results and S. E. Brockerhoff, personal communication).…”

Synaptojanin 1-linked phosphoinositide dyshomeostasis and cognitive deficits in mouse models of Down's syndrome

“…Genetic ablation of these enzymes in the mouse leads to early postnatal lethality likely caused by defects in neurotransmission (3,4). The critical importance of synaptojanin 1 at synapses is corroborated by genetic studies in worms, flies, and zebrafish (5)(6)(7).…”