Reim, K. et al. Structurally and functionally unique complexins at retinal ribbon synapses. J. Cell Biol. 169, 669-680

Baylor College of Medicine, Houston, Texas, United States
The Journal of Cell Biology (Impact Factor: 9.83). 06/2005; 169(4):669-80. DOI: 10.1083/jcb.200502115
Source: PubMed


Ribbon synapses in retinal sensory neurons maintain large pools of readily releasable synaptic vesicles. This allows them to release several hundreds of vesicles per second at every presynaptic release site. The molecular components that cause this high transmitter release efficiency of ribbon synapses are unknown. In the present study, we identified and characterized two novel vertebrate complexins (CPXs), CPXs III and IV, that are the only CPX isoforms present in retinal ribbon synapses. CPXs III and IV are COOH-terminally farnesylated, and, like CPXs I and II, bind to SNAP receptor complexes. CPXs III and IV can functionally replace CPXs I and II, and their COOH-terminal farnesylation regulates their synaptic targeting and modulatory function in transmitter release. The novel CPXs III and IV may contribute to the unique release efficacy of retinal sensory neurons.

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    • "Most AZ proteins come in synapse specific isoforms and/or splice variants with specialized properties adapted to the individual needs in neurotransmission at different synapse types. In line with this, the continuously active retinal photoreceptor ribbon synapses contain a unique set of presynaptic proteins and protein variants, e.g., Syntaxin 3, RIBEYE, Complexins 3 and 4, and ubMunc13-2 (Morgans et al., 1996; Schmitz et al., 2000; Reim et al., 2005; Cooper et al., 2012). Recently, we showed that Piccolino, a splice variant of the CAZ protein Piccolo, is specifically present at ribbon-type synapses, and absent at conventional chemical synapses (Regus-Leidig et al., 2013). "
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    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.
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    • "Complexin 4 (Cplx4) is one of the few proteins involved in vesicle exocytosis that is also established as a specific marker for photoreceptor ribbon synapses (see for review [1]). Cplx4 is expressed in rod synapses [36] and is responsible for binding and stabilizing assembled SNARE complexes during Ca2+-triggered fusion of synaptic vesicles [36], [37]. The expression of this protein was preserved in rod synapses in the CaV1.4(α1F)-KO at all investigated ages. "
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    ABSTRACT: Several studies have shown the importance of calcium channels in the development and/or maturation of synapses. The CaV1.4(α1F) knockout mouse is a unique model to study the role of calcium channels in photoreceptor synapse formation. It features abnormal ribbon synapses and aberrant cone morphology. We investigated the expression and targeting of several key elements of ribbon synapses and analyzed the cone morphology in the CaV1.4(α1F) knockout retina. Our data demonstrate that most abnormalities occur after eye opening. Indeed, scaffolding proteins such as Bassoon and RIM2 are properly targeted at first, but their expression and localization are not maintained in adulthood. This indicates that either calcium or the CaV1.4 channel, or both are necessary for the maintenance of their normal expression and distribution in photoreceptors. Other proteins, such as Veli3 and PSD-95, also display abnormal expression in rods prior to eye opening. Conversely, vesicle related proteins appear normal. Our data demonstrate that the CaV1.4 channel is important for maintaining scaffolding proteins in the ribbon synapse but less vital for proteins related to vesicular release. This study also confirms that in adult retinae, cones show developmental features such as sprouting and synaptogenesis. Overall we present evidence that in the absence of the CaV1.4 channel, photoreceptor synapses remain immature and are unable to stabilize.
    Full-text · Article · May 2013 · PLoS ONE
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    • "This downregulation may be caused by a reduction in the insulin level owing to decreased expression of Pcsk1, and may also be due to increased expression of Ide, which degrades insulin and/or Aβ peptides in a competitive fashion (Farris et al. 2003). Moreover, genes involved in insulin secretion, such as Vgf (Watson et al. 2005) and Cplx3 (Reim et al. 2005), were also found to be downregulated in 3xTg-AD mice in the present study (Fig. 4B), suggesting that AD pathology diminishes the production and secretion of insulin in brain. "
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