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Jocelyn E Shaw - One of the best experts on this subject based on the ideXlab platform.

  • Interactions between innexins UNC-7 and UNC-9 mediate Electrical Synapse specificity in the Caenorhabditis elegans locomotory nervous system
    Neural Development, 2009
    Co-Authors: Todd A Starich, I Martha Skerrett, Bruce J Nicholson, Jocelyn E Shaw
    Abstract:

    Background Approximately 10% of Caenorhabditis elegans nervous system Synapses are Electrical, that is, gap junctions composed of innexins. The locomotory nervous system consists of several pairs of interneurons and three major classes of motor neurons, all with stereotypical patterns of connectivity that include gap junctions. Mutations in the two innexin genes unc-7 and unc-9 result in identical uncoordinated movement phenotypes, and their respective gene products were investigated for their contribution to Electrical Synapse connectivity. Results unc-7 encodes three innexin isoforms. Two of these, UNC-7S and UNC-7SR, are functionally equivalent and play an essential role in coordinated locomotion. UNC-7S and UNC-7SR are widely expressed and co-localize extensively with green fluorescent protein-tagged innexin UNC-9 in the ventral and dorsal nerve cords. A subset of UNC-7S/SR expression visualizes gap junctions formed between the AVB forward command interneurons and their B class motor neuron partners. Experiments indicate that expression of UNC-7S/SR in AVB and expression of UNC-9 in B motor neurons is necessary for these gap junctions to form. In Xenopus oocyte pairs, both UNC-7S and UNC-9 form homomeric gap junctions, and together they form heterotypic channels. Xenopus oocyte studies and co-localization studies in C. elegans suggest that UNC-7S and UNC-9 do not heteromerize in the same hemichannel, leading to the model that hemichannels in AVB:B motor neuron gap junctions are homomeric and heterotypic. Conclusion UNC-7S and UNC-9 are widely expressed and contribute to a large number of the gap junctions identified in the locomotory nervous system. Proper AVB:B gap junction formation requires UNC-7S expression in AVB interneurons and UNC-9 expression in B motor neurons. More broadly, this illustrates that innexin identity is critical for Electrical Synapse specificity, but differential (compartmentalized) innexin expression cannot account for all of the specificity seen in C. elegans , and other factors must influence the determination of synaptic partners.

  • interactions between innexins unc 7 and unc 9 mediate Electrical Synapse specificity in the caenorhabditis elegans locomotory nervous system
    Neural Development, 2009
    Co-Authors: Todd A Starich, Bruce J Nicholson, Martha I Skerrett, Jocelyn E Shaw
    Abstract:

    Approximately 10% of Caenorhabditis elegans nervous system Synapses are Electrical, that is, gap junctions composed of innexins. The locomotory nervous system consists of several pairs of interneurons and three major classes of motor neurons, all with stereotypical patterns of connectivity that include gap junctions. Mutations in the two innexin genes unc-7 and unc-9 result in identical uncoordinated movement phenotypes, and their respective gene products were investigated for their contribution to Electrical Synapse connectivity. unc-7 encodes three innexin isoforms. Two of these, UNC-7S and UNC-7SR, are functionally equivalent and play an essential role in coordinated locomotion. UNC-7S and UNC-7SR are widely expressed and co-localize extensively with green fluorescent protein-tagged innexin UNC-9 in the ventral and dorsal nerve cords. A subset of UNC-7S/SR expression visualizes gap junctions formed between the AVB forward command interneurons and their B class motor neuron partners. Experiments indicate that expression of UNC-7S/SR in AVB and expression of UNC-9 in B motor neurons is necessary for these gap junctions to form. In Xenopus oocyte pairs, both UNC-7S and UNC-9 form homomeric gap junctions, and together they form heterotypic channels. Xenopus oocyte studies and co-localization studies in C. elegans suggest that UNC-7S and UNC-9 do not heteromerize in the same hemichannel, leading to the model that hemichannels in AVB:B motor neuron gap junctions are homomeric and heterotypic. UNC-7S and UNC-9 are widely expressed and contribute to a large number of the gap junctions identified in the locomotory nervous system. Proper AVB:B gap junction formation requires UNC-7S expression in AVB interneurons and UNC-9 expression in B motor neurons. More broadly, this illustrates that innexin identity is critical for Electrical Synapse specificity, but differential (compartmentalized) innexin expression cannot account for all of the specificity seen in C. elegans, and other factors must influence the determination of synaptic partners.

Todd A Starich - One of the best experts on this subject based on the ideXlab platform.

  • Interactions between innexins UNC-7 and UNC-9 mediate Electrical Synapse specificity in the Caenorhabditis elegans locomotory nervous system
    Neural Development, 2009
    Co-Authors: Todd A Starich, I Martha Skerrett, Bruce J Nicholson, Jocelyn E Shaw
    Abstract:

    Background Approximately 10% of Caenorhabditis elegans nervous system Synapses are Electrical, that is, gap junctions composed of innexins. The locomotory nervous system consists of several pairs of interneurons and three major classes of motor neurons, all with stereotypical patterns of connectivity that include gap junctions. Mutations in the two innexin genes unc-7 and unc-9 result in identical uncoordinated movement phenotypes, and their respective gene products were investigated for their contribution to Electrical Synapse connectivity. Results unc-7 encodes three innexin isoforms. Two of these, UNC-7S and UNC-7SR, are functionally equivalent and play an essential role in coordinated locomotion. UNC-7S and UNC-7SR are widely expressed and co-localize extensively with green fluorescent protein-tagged innexin UNC-9 in the ventral and dorsal nerve cords. A subset of UNC-7S/SR expression visualizes gap junctions formed between the AVB forward command interneurons and their B class motor neuron partners. Experiments indicate that expression of UNC-7S/SR in AVB and expression of UNC-9 in B motor neurons is necessary for these gap junctions to form. In Xenopus oocyte pairs, both UNC-7S and UNC-9 form homomeric gap junctions, and together they form heterotypic channels. Xenopus oocyte studies and co-localization studies in C. elegans suggest that UNC-7S and UNC-9 do not heteromerize in the same hemichannel, leading to the model that hemichannels in AVB:B motor neuron gap junctions are homomeric and heterotypic. Conclusion UNC-7S and UNC-9 are widely expressed and contribute to a large number of the gap junctions identified in the locomotory nervous system. Proper AVB:B gap junction formation requires UNC-7S expression in AVB interneurons and UNC-9 expression in B motor neurons. More broadly, this illustrates that innexin identity is critical for Electrical Synapse specificity, but differential (compartmentalized) innexin expression cannot account for all of the specificity seen in C. elegans , and other factors must influence the determination of synaptic partners.

  • interactions between innexins unc 7 and unc 9 mediate Electrical Synapse specificity in the caenorhabditis elegans locomotory nervous system
    Neural Development, 2009
    Co-Authors: Todd A Starich, Bruce J Nicholson, Martha I Skerrett, Jocelyn E Shaw
    Abstract:

    Approximately 10% of Caenorhabditis elegans nervous system Synapses are Electrical, that is, gap junctions composed of innexins. The locomotory nervous system consists of several pairs of interneurons and three major classes of motor neurons, all with stereotypical patterns of connectivity that include gap junctions. Mutations in the two innexin genes unc-7 and unc-9 result in identical uncoordinated movement phenotypes, and their respective gene products were investigated for their contribution to Electrical Synapse connectivity. unc-7 encodes three innexin isoforms. Two of these, UNC-7S and UNC-7SR, are functionally equivalent and play an essential role in coordinated locomotion. UNC-7S and UNC-7SR are widely expressed and co-localize extensively with green fluorescent protein-tagged innexin UNC-9 in the ventral and dorsal nerve cords. A subset of UNC-7S/SR expression visualizes gap junctions formed between the AVB forward command interneurons and their B class motor neuron partners. Experiments indicate that expression of UNC-7S/SR in AVB and expression of UNC-9 in B motor neurons is necessary for these gap junctions to form. In Xenopus oocyte pairs, both UNC-7S and UNC-9 form homomeric gap junctions, and together they form heterotypic channels. Xenopus oocyte studies and co-localization studies in C. elegans suggest that UNC-7S and UNC-9 do not heteromerize in the same hemichannel, leading to the model that hemichannels in AVB:B motor neuron gap junctions are homomeric and heterotypic. UNC-7S and UNC-9 are widely expressed and contribute to a large number of the gap junctions identified in the locomotory nervous system. Proper AVB:B gap junction formation requires UNC-7S expression in AVB interneurons and UNC-9 expression in B motor neurons. More broadly, this illustrates that innexin identity is critical for Electrical Synapse specificity, but differential (compartmentalized) innexin expression cannot account for all of the specificity seen in C. elegans, and other factors must influence the determination of synaptic partners.

John Obrien - One of the best experts on this subject based on the ideXlab platform.

  • calmodulin binding to connexin 35 specializations to function as an Electrical Synapse
    International Journal of Molecular Sciences, 2020
    Co-Authors: Jaya Aseervatham, Cheryl K Mitchell, Yaping Lin, Ruth Heidelberger, John Obrien
    Abstract:

    Calmodulin binding is a nearly universal property of gap junction proteins, imparting a calcium-dependent uncoupling behavior that can serve in an emergency to decouple a stressed cell from its neighbors. However, gap junctions that function as Electrical Synapses within networks of neurons routinely encounter large fluctuations in local cytoplasmic calcium concentration; frequent uncoupling would be impractical and counterproductive. We have studied the properties and functional consequences of calmodulin binding to the Electrical Synapse protein Connexin 35 (Cx35 or gjd2b), homologous to mammalian Connexin 36 (Cx36 or gjd2). We find that specializations in Cx35 calmodulin binding sites make it relatively impervious to moderately high levels of cytoplasmic calcium. Calmodulin binding to a site in the C-terminus causes uncoupling when calcium reaches low micromolar concentrations, a behavior prevented by mutations that eliminate calmodulin binding. However, milder stimuli promote calcium/calmodulin-dependent protein kinase II activity that potentiates coupling without interference from calmodulin binding. A second calmodulin binding site in the end of the Cx35 cytoplasmic loop, homologous to a calmodulin binding site present in many connexins, binds calmodulin with very low affinity and stoichiometry. Together, the calmodulin binding sites cause Cx35 to uncouple only at extreme levels of intracellular calcium.

  • zebrafish connexin 79 8 gja8a a lens connexin used as an Electrical Synapse in some neurons
    Developmental Neurobiology, 2017
    Co-Authors: Shunichi Yoshikawa, Cheryl K Mitchell, Yaping Lin, Alejandro Vila, Jasmin Segelken, Duc Nguyen, John Obrien
    Abstract:

    In the mammalian central nervous system, a remarkably small number of connexins is used in Electrical Synapses, with the majority formed from Cx36. A larger number has been detected in teleosts, with some seeming to serve restricted roles. Here, we report the discovery of a new connexin expressed in the zebrafish lens and a limited set of neurons. Zebrafish cx79.8 (gja8a), previously annotated incorrectly as cx50.5 based on a partial cDNA sequence, is a homologue of mammalian Cx50 (Gja8). We examined its expression through transgenic promoter-reporter constructs, in situ hybridization, and immunolabeling, and examined regulation of coupling in transfected HeLa cells. cx79.8 was expressed most strongly in the lens, but expression was also found in several groups of neurons in the cerebellum and related areas at the midbrain-hindbrain boundary, in cone photoreceptors, and in neurons in the retinal inner nuclear and ganglion cell layers. Labeling in the retina with antibodies against two C-terminal epitopes revealed numerous small punctate spots in the inner plexiform layer and along the somata of cones. Abundant gap junctions were labeled in the outer 1/3 of the lens, but were absent from the center, suggesting that the epitopes or the entire protein was absent from the center. Cx79.8 tracer coupling was strongly regulated by phosphorylation, and was extremely low in control conditions in HeLa cells due to protein phosphatase 2A activity. These properties allow coupling to be strongly restricted in situ, a frequently observed property for Electrical Synapses. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 548-561, 2017.

  • the ever changing Electrical Synapse
    Current Opinion in Neurobiology, 2014
    Co-Authors: John Obrien
    Abstract:

    A wealth of research has revealed that Electrical Synapses in the central nervous system exhibit a high degree of plasticity. Several recent studies, particularly in the retina and inferior olive, highlight this plasticity. Three classes of mechanisms can alter Electrical coupling over time courses ranging from milliseconds to days. Changes of membrane conductance through synaptic input or spiking activity shunt current and decouple neurons on the millisecond time scale. Such activity can also alter coupling symmetry, rectifying Electrical Synapses. More stable rectification can be accomplished through molecular asymmetry of the Synapse itself. On the minutes time scale, changes in connexin phosphorylation can change coupling quasi-stably with an order of magnitude dynamic range. On the hours to days time scale, changes in expression level of connexins alter coupling through the course of circadian time, over developmental time, or in response to tissue injury. Combined, all of these mechanisms allow Electrical coupling to be highly dynamic, changing in response to demands at the whole network level, in small portions of a network, or at the level of an individual Synapse.

  • molecular and functional asymmetry at a vertebrate Electrical Synapse
    Neuron, 2013
    Co-Authors: John E Rash, John Obrien, Sebastian Curti, Kimberly G Vanderpool, Naomi Kamasawa, Srikant Nannapaneni, Nicolas Palaciosprado, Carmen E Flores, Thomas Yasumura, B D Lynn
    Abstract:

    Electrical Synapses are abundant in the vertebrate brain, but their functional and molecular complexities are still poorly understood. We report here that Electrical Synapses between auditory afferents and goldfish Mauthner cells are constructed by apposition of hemichannels formed by two homologs of mammalian connexin 36 (Cx36) and that, while Cx35 is restricted to presynaptic hemiplaques, Cx34.7 is restricted to postsynaptic hemiplaques, forming heterotypic junctions. This molecular asymmetry is associated with rectification of Electrical transmission that may act to promote cooperativity between auditory afferents. Our data suggest that, in similarity to pre- and postsynaptic sites at chemical Synapses, one side in Electrical Synapses should not necessarily be considered the mirror image of the other. While asymmetry based on the presence of two Cx36 homologs is restricted to teleost fish, it might also be based on differences in posttranslational modifications of individual connexins or in the complement of gap junction-associated proteins.

Bruce J Nicholson - One of the best experts on this subject based on the ideXlab platform.

  • Interactions between innexins UNC-7 and UNC-9 mediate Electrical Synapse specificity in the Caenorhabditis elegans locomotory nervous system
    Neural Development, 2009
    Co-Authors: Todd A Starich, I Martha Skerrett, Bruce J Nicholson, Jocelyn E Shaw
    Abstract:

    Background Approximately 10% of Caenorhabditis elegans nervous system Synapses are Electrical, that is, gap junctions composed of innexins. The locomotory nervous system consists of several pairs of interneurons and three major classes of motor neurons, all with stereotypical patterns of connectivity that include gap junctions. Mutations in the two innexin genes unc-7 and unc-9 result in identical uncoordinated movement phenotypes, and their respective gene products were investigated for their contribution to Electrical Synapse connectivity. Results unc-7 encodes three innexin isoforms. Two of these, UNC-7S and UNC-7SR, are functionally equivalent and play an essential role in coordinated locomotion. UNC-7S and UNC-7SR are widely expressed and co-localize extensively with green fluorescent protein-tagged innexin UNC-9 in the ventral and dorsal nerve cords. A subset of UNC-7S/SR expression visualizes gap junctions formed between the AVB forward command interneurons and their B class motor neuron partners. Experiments indicate that expression of UNC-7S/SR in AVB and expression of UNC-9 in B motor neurons is necessary for these gap junctions to form. In Xenopus oocyte pairs, both UNC-7S and UNC-9 form homomeric gap junctions, and together they form heterotypic channels. Xenopus oocyte studies and co-localization studies in C. elegans suggest that UNC-7S and UNC-9 do not heteromerize in the same hemichannel, leading to the model that hemichannels in AVB:B motor neuron gap junctions are homomeric and heterotypic. Conclusion UNC-7S and UNC-9 are widely expressed and contribute to a large number of the gap junctions identified in the locomotory nervous system. Proper AVB:B gap junction formation requires UNC-7S expression in AVB interneurons and UNC-9 expression in B motor neurons. More broadly, this illustrates that innexin identity is critical for Electrical Synapse specificity, but differential (compartmentalized) innexin expression cannot account for all of the specificity seen in C. elegans , and other factors must influence the determination of synaptic partners.

  • interactions between innexins unc 7 and unc 9 mediate Electrical Synapse specificity in the caenorhabditis elegans locomotory nervous system
    Neural Development, 2009
    Co-Authors: Todd A Starich, Bruce J Nicholson, Martha I Skerrett, Jocelyn E Shaw
    Abstract:

    Approximately 10% of Caenorhabditis elegans nervous system Synapses are Electrical, that is, gap junctions composed of innexins. The locomotory nervous system consists of several pairs of interneurons and three major classes of motor neurons, all with stereotypical patterns of connectivity that include gap junctions. Mutations in the two innexin genes unc-7 and unc-9 result in identical uncoordinated movement phenotypes, and their respective gene products were investigated for their contribution to Electrical Synapse connectivity. unc-7 encodes three innexin isoforms. Two of these, UNC-7S and UNC-7SR, are functionally equivalent and play an essential role in coordinated locomotion. UNC-7S and UNC-7SR are widely expressed and co-localize extensively with green fluorescent protein-tagged innexin UNC-9 in the ventral and dorsal nerve cords. A subset of UNC-7S/SR expression visualizes gap junctions formed between the AVB forward command interneurons and their B class motor neuron partners. Experiments indicate that expression of UNC-7S/SR in AVB and expression of UNC-9 in B motor neurons is necessary for these gap junctions to form. In Xenopus oocyte pairs, both UNC-7S and UNC-9 form homomeric gap junctions, and together they form heterotypic channels. Xenopus oocyte studies and co-localization studies in C. elegans suggest that UNC-7S and UNC-9 do not heteromerize in the same hemichannel, leading to the model that hemichannels in AVB:B motor neuron gap junctions are homomeric and heterotypic. UNC-7S and UNC-9 are widely expressed and contribute to a large number of the gap junctions identified in the locomotory nervous system. Proper AVB:B gap junction formation requires UNC-7S expression in AVB interneurons and UNC-9 expression in B motor neurons. More broadly, this illustrates that innexin identity is critical for Electrical Synapse specificity, but differential (compartmentalized) innexin expression cannot account for all of the specificity seen in C. elegans, and other factors must influence the determination of synaptic partners.

Peter R Stern - One of the best experts on this subject based on the ideXlab platform.

  • Electrical Synapse plasticity
    Science Signaling, 2011
    Co-Authors: Peter R Stern
    Abstract:

    Communication via Electrical Synapses is an important and fast local mechanism. However, very little is known about use-dependent plasticity in the efficacy and rectification properties of Electrical Synapses. Haas et al. (see the Perspective by Hestrin) examined gap-junction communication in the reticular nucleus of the thalamus. Induced burst firing in pairs of coupled thalamic reticular nucleus neurons in vitro resulted in long-term depression. The changes in gap-junctional communication were also asymmetric, depending on the strength of the burst. Such modification of Electrical Synapses resulting from activity in coupled neurons is likely to be a widespread and powerful mechanism for the reorganization of Electrically coupled networks. J. S. Haas, B. Zavala, C. E. Landisman, Activity-dependent long-term depression of Electrical Synapses. Science 334 , 389–393 (2011). [Abstract][Full Text] S. Hestrin, The strength of Electrical Synapses. Science 334 , 315–316 (2011). [Abstract][Full Text]