An interaction of heart disease-associated proteins POPDC1/2 with XIRP1 in transverse tubules and intercalated discs

Ian Holt, Heidi R. Fuller, Roland F. R. Schindler, Sally L. Shirran, Thomas Brand, Glenn E. Morris

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

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.
Original languageEnglish
Article number88
Number of pages13
JournalBMC Molecular and Cell Biology
Volume21
DOIs
Publication statusPublished - 1 Dec 2020

Keywords

  • Popeye domain-containing
  • Xin actin binding repeat-containing
  • Cardiac conduction
  • Intercalated discs
  • Transverse tubes

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