Abstract
BackgroundPopeye 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.ResultsThere 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.ConclusionsMutations 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.
Highlights
Popeye domain-containing proteins 1 and 2 (POPDC1 and Popeye Domain Containing 2 (POPDC2)) are transmembrane proteins involved in cyclic AMP-mediated signalling processes and are required for normal cardiac pacemaking and conduction
Human Popeye domain containing protein 1 (POPDC1) is found on chromosome 6q21 along with Popeye Domain Containing 3 (POPDC3) in tandem array, whereas POPDC2 is found on human chromosome 3q13.33
Cardiac actin and Xin Actin Binding Repeat Containing 1 (XIRP1) had the highest scores for a number of significant peptides identified by mass spectrometry (Table 1) for both mouse POPDC1 and mouse POPDC2, after eliminating nonspecific binding of proteins to control beads
Summary
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. Popeye domain containing protein 1 (POPDC1), known as blood vessel epicardial substance (BVES), was first found in chicken heart by subtractive hybridisation [1, 2]. Popdc and two related gene family members, Popdc and Popdc, were identified in mammals and shown to be developmentally regulated and preferentially expressed in cardiac and skeletal muscle [2]. Interaction between POPDC proteins and the potassium two pore domain channel subfamily K member 2 (KCNK2, known as TREK-1) has been demonstrated, which leads to an increase in KCNK2
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