An interaction of heart disease-associated proteins POPDC1/2 with XIRP1 in transverse tubules and intercalated discs
Abstract
Background : Popeye domain-containing proteins 1 and 2 (POPDC1 and POPDC2) are transmembrane proteins involved in cyclic AMP-mediated signalling processes and are required for normal cardiac pacemaking and conduction. In order to identify novel protein interaction partners, POPDC1 and 2 proteins were attached to beads and compared by proteomic analysis with control beads in the pull-down of proteins from cultured human skeletal myotubes. Results : There were highly-significant interactions of both POPDC1 and POPDC2 with XIRP1 (Xin actin binding repeat-containing protein 1), actin and, to a lesser degree, annexin A5. In adult human skeletal muscle, both XIRP1 and POPDC1/2 were present at the sarcolemma and in T-tubules. The interaction of POPDC1 with XIRP1 was confirmed in adult rat heart extracts. Using new monoclonal antibodies specific for POPDC1 and POPDC2, both proteins, together with XIRP1, were found mainly at intercalated discs but also at T-tubules in adult rat and human heart. Conclusions : Mutations in human POPDC1, POPDC2 and in human XIRP1, all cause pathological cardiac arrhythmias, suggesting a possible role for POPDC1/2 and XIRP1 interaction in normal cardiac conduction.
Citation
Holt , I , Fuller , H R , Schindler , R F R , Shirran , S L , Brand , T & Morris , G E 2020 , ' An interaction of heart disease-associated proteins POPDC1/2 with XIRP1 in transverse tubules and intercalated discs ' , BMC Molecular and Cell Biology , vol. 21 , 88 . https://doi.org/10.1186/s12860-020-00329-3
Publication
BMC Molecular and Cell Biology
Status
Peer reviewed
ISSN
2661-8850Type
Journal article
Rights
Copyright © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
Description
This work was supported by the British Heart Foundation [PG/16/68/31991; to IH and GEM], [PG/19/13/34247; to TB] and the Orthopaedic Institute Ltd., RJAH Orthopaedic Hospital, Oswestry UK [RPG141 and RPG189; to IH and GEM].Collections
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