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http://purl.uniprot.org/citations/25139742http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25139742http://www.w3.org/2000/01/rdf-schema#comment"

Aims

It is well known that connexin43 (Cx43) forms gap junctions. We recently showed that Cx43 is also part of a protein-interacting network that regulates excitability. Cardiac-specific truncation of Cx43 C-terminus (mutant 'Cx43D378stop') led to lethal arrhythmias. Cx43D378stop localized to the intercalated disc (ID); cell-cell coupling was normal, but there was significant sodium current (INa) loss. We proposed that the microtubule plus-end is at the crux of the Cx43-INa relation. Yet, specific localization of relevant molecular players was prevented due to the resolution limit of fluorescence microscopy. Here, we use nanoscale imaging to establish: (i) the morphology of clusters formed by the microtubule plus-end tracking protein 'end-binding 1' (EB1), (ii) their position, and that of sodium channel alpha-subunit NaV1.5, relative to N-cadherin-rich sites, and (iii) the role of Cx43 C-terminus on the above-mentioned parameters and on the location-specific function of INa.

Methods and results

Super-resolution fluorescence localization microscopy in murine adult cardiomyocytes revealed EB1 and NaV1.5 as distinct clusters preferentially localized to N-cadherin-rich sites. Extent of co-localization decreased in Cx43D378stop cells. Macropatch and scanning patch clamp showed reduced INa exclusively at cell end, without changes in unitary conductance. Experiments in Cx43-modified HL1 cells confirmed the relation between Cx43, INa, and microtubules.

Conclusions

NaV1.5 and EB1 localization at the cell end is Cx43-dependent. Cx43 is part of a molecular complex that determines capture of the microtubule plus-end at the ID, facilitating cargo delivery. These observations link excitability and electrical coupling through a common molecular mechanism."xsd:string
http://purl.uniprot.org/citations/25139742http://purl.org/dc/terms/identifier"doi:10.1093/cvr/cvu195"xsd:string
http://purl.uniprot.org/citations/25139742http://purl.uniprot.org/core/author"Li Z."xsd:string
http://purl.uniprot.org/citations/25139742http://purl.uniprot.org/core/author"Lin X."xsd:string
http://purl.uniprot.org/citations/25139742http://purl.uniprot.org/core/author"Zhang M."xsd:string
http://purl.uniprot.org/citations/25139742http://purl.uniprot.org/core/author"Keegan S."xsd:string
http://purl.uniprot.org/citations/25139742http://purl.uniprot.org/core/author"Delmar M."xsd:string
http://purl.uniprot.org/citations/25139742http://purl.uniprot.org/core/author"Rothenberg E."xsd:string
http://purl.uniprot.org/citations/25139742http://purl.uniprot.org/core/author"Fenyo D."xsd:string
http://purl.uniprot.org/citations/25139742http://purl.uniprot.org/core/author"Willecke K."xsd:string
http://purl.uniprot.org/citations/25139742http://purl.uniprot.org/core/author"Liang F.X."xsd:string
http://purl.uniprot.org/citations/25139742http://purl.uniprot.org/core/author"Leo-Macias A."xsd:string
http://purl.uniprot.org/citations/25139742http://purl.uniprot.org/core/author"Pfenniger A."xsd:string
http://purl.uniprot.org/citations/25139742http://purl.uniprot.org/core/author"Lubkemeier I."xsd:string
http://purl.uniprot.org/citations/25139742http://purl.uniprot.org/core/author"Agullo-Pascual E."xsd:string
http://purl.uniprot.org/citations/25139742http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/25139742http://purl.uniprot.org/core/name"Cardiovasc Res"xsd:string
http://purl.uniprot.org/citations/25139742http://purl.uniprot.org/core/pages"371-381"xsd:string
http://purl.uniprot.org/citations/25139742http://purl.uniprot.org/core/title"Super-resolution imaging reveals that loss of the C-terminus of connexin43 limits microtubule plus-end capture and NaV1.5 localization at the intercalated disc."xsd:string
http://purl.uniprot.org/citations/25139742http://purl.uniprot.org/core/volume"104"xsd:string
http://purl.uniprot.org/citations/25139742http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/25139742
http://purl.uniprot.org/citations/25139742http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/25139742
http://purl.uniprot.org/uniprot/#_D3YXW2-mappedCitation-25139742http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25139742
http://purl.uniprot.org/uniprot/#_A0A0R4J1M7-mappedCitation-25139742http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25139742
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