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      A genetic basis for molecular asymmetry at vertebrate electrical synapses

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          Abstract

          Neural network function is based upon the patterns and types of connections made between neurons. Neuronal synapses are adhesions specialized for communication and they come in two types, chemical and electrical. Communication at chemical synapses occurs via neurotransmitter release whereas electrical synapses utilize gap junctions for direct ionic and metabolic coupling. Electrical synapses are often viewed as symmetrical structures, with the same components making both sides of the gap junction. By contrast, we show that a broad set of electrical synapses in zebrafish, Danio rerio, require two gap-junction-forming Connexins for formation and function. We find that one Connexin functions presynaptically while the other functions postsynaptically in forming the channels. We also show that these synapses are required for the speed and coordination of escape responses. Our data identify a genetic basis for molecular asymmetry at vertebrate electrical synapses and show they are required for appropriate behavioral performance.

          DOI: http://dx.doi.org/10.7554/eLife.25364.001

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          Most cited references51

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          A transcription activator-like effector toolbox for genome engineering.

          Transcription activator-like effectors (TALEs) are a class of naturally occurring DNA-binding proteins found in the plant pathogen Xanthomonas sp. The DNA-binding domain of each TALE consists of tandem 34-amino acid repeat modules that can be rearranged according to a simple cipher to target new DNA sequences. Customized TALEs can be used for a wide variety of genome engineering applications, including transcriptional modulation and genome editing. Here we describe a toolbox for rapid construction of custom TALE transcription factors (TALE-TFs) and nucleases (TALENs) using a hierarchical ligation procedure. This toolbox facilitates affordable and rapid construction of custom TALE-TFs and TALENs within 1 week and can be easily scaled up to construct TALEs for multiple targets in parallel. We also provide details for testing the activity in mammalian cells of custom TALE-TFs and TALENs using quantitative reverse-transcription PCR and Surveyor nuclease, respectively. The TALE toolbox described here will enable a broad range of biological applications.
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            Electrical synapses and their functional interactions with chemical synapses.

            E. Pereda (2014)
            Brain function relies on the ability of neurons to communicate with each other. Interneuronal communication primarily takes place at synapses, where information from one neuron is rapidly conveyed to a second neuron. There are two main modalities of synaptic transmission: chemical and electrical. Far from functioning independently and serving unrelated functions, mounting evidence indicates that these two modalities of synaptic transmission closely interact, both during development and in the adult brain. Rather than conceiving synaptic transmission as either chemical or electrical, this article emphasizes the notion that synaptic transmission is both chemical and electrical, and that interactions between these two forms of interneuronal communication might be required for normal brain development and function.
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              • Article: not found

              Gap junctions.

              Gap junctions are aggregates of intercellular channels that permit direct cell-cell transfer of ions and small molecules. Initially described as low-resistance ion pathways joining excitable cells (nerve and muscle), gap junctions are found joining virtually all cells in solid tissues. Their long evolutionary history has permitted adaptation of gap-junctional intercellular communication to a variety of functions, with multiple regulatory mechanisms. Gap-junctional channels are composed of hexamers of medium-sized families of integral proteins: connexins in chordates and innexins in precordates. The functions of gap junctions have been explored by studying mutations in flies, worms, and humans, and targeted gene disruption in mice. These studies have revealed a wide diversity of function in tissue and organ biology.
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                Author and article information

                Contributors
                Role: Reviewing editor
                Journal
                eLife
                Elife
                eLife
                eLife
                eLife
                eLife Sciences Publications, Ltd
                2050-084X
                22 May 2017
                2017
                : 6
                : e25364
                Affiliations
                [1 ]deptDivision of Basic Sciences , Fred Hutchinson Cancer Research Center , Seattle, United States
                [2 ]deptDepartment of Cell and Developmental Biology , University of Pennsylvania Perelman School of Medicine , Philadelphia, United States
                [3 ]deptDepartment of Ophthalmology and Visual Science, McGovern Medical School , University of Texas Health Sciences Center at Houston , Houston, United States
                University of California, Berkeley , United States
                University of California, Berkeley , United States
                Author notes
                [‡]

                Institute of Neuroscience, University of Oregon, Eugene, United States.

                [†]

                These authors contributed equally to this work.

                Author information
                http://orcid.org/0000-0001-7519-3677
                http://orcid.org/0000-0002-9178-1636
                http://orcid.org/0000-0002-0270-3442
                Article
                25364
                10.7554/eLife.25364
                5462537
                28530549
                2cc883e1-bdf0-47eb-9c8d-f60b19480d39
                © 2017, Miller et al

                This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

                History
                : 24 January 2017
                : 20 May 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000065, National Institute of Neurological Disorders and Stroke;
                Award ID: F32NS074839
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000025, National Institute of Mental Health;
                Award ID: R01MH109498
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000053, National Eye Institute;
                Award ID: R01EY012857
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100009633, Eunice Kennedy Shriver National Institute of Child Health and Human Development;
                Award ID: R01HD076585
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000065, National Institute of Neurological Disorders and Stroke;
                Award ID: R21NS076950
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000065, National Institute of Neurological Disorders and Stroke;
                Award ID: K99/R00NS085035
                Award Recipient :
                The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
                Categories
                Research Article
                Neuroscience
                Custom metadata
                2.5
                Electrical synapses are neuronal, gap-junction-based connections found throughout the nervous system that, in the escape circuit of zebrafish, are composed of molecularly distinct pre- and postsynaptic junction forming proteins that are required for behavioral performance.

                Life sciences
                electrical synapse,synaptogenesis,neural circuit wiring,behavior,connexins,zebrafish
                Life sciences
                electrical synapse, synaptogenesis, neural circuit wiring, behavior, connexins, zebrafish

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