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Under Construction: Building the Macromolecular Superstructure and Signaling Components of an Electrical Synapse

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Abstract

A great deal is now known about the protein components of tight junctions and adherens junctions, as well as how these are assembled. Less is known about the molecular framework of gap junctions, but these also have membrane specializations and are subject to regulation of their assembly and turnover. Thus, it is reasonable to consider that these three types of junctions may share macromolecular commonalities. Indeed, the tight junction scaffolding protein zonula occluden-1 (ZO-1) is also present at adherens and gap junctions, including neuronal gap junctions. On the basis of these earlier observations, we more recently found that two additional proteins, AF6 and MUPP1, known to be associated with ZO-1 at tight and adherens junctions, are also components of neuronal gap junctions in rodent brain and directly interact with connexin36 (Cx36) that forms these junctions. Here, we show by immunofluorescence labeling that the cytoskeletal-associated protein cingulin, commonly found at tight junctions, is also localized at neuronal gap junctions throughout the central nervous system. In consideration of known functions related to ZO-1, AF6, MUPP1, and cingulin, our results provide a context in which to examine functional relationships between these proteins at Cx36-containing electrical synapses in brain—specifically, how they may contribute to regulation of transmission at these synapses, and how they may govern gap junction channel assembly and/or disassembly.

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Acknowledgments

Supported in part by grants from the Canadian Institutes of Health Research (MOP 106598) to J.I.N., and from the National Institutes of Health (NS31027, NS44010, NS44395) to J. E. Rash with a subaward to J.I.N. We thank B. McLean for excellent technical assistance.

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  1. Xinbo Li

    Present address: Casey Eye Institute, Oregon Health and Science University, Portland, OR, USA

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  1. Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, MB, R3E 0J9, Canada

    B. D. Lynn, Xinbo Li & J. I. Nagy

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  1. B. D. Lynn
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Correspondence to J. I. Nagy.

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B. D. Lynn and Xinbo Li contributed equally to this study.

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Lynn, B.D., Li, X. & Nagy, J.I. Under Construction: Building the Macromolecular Superstructure and Signaling Components of an Electrical Synapse. J Membrane Biol 245, 303–317 (2012). https://doi.org/10.1007/s00232-012-9451-5

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