The cardiac conduction system relies on Purkinje cells, which ensure the rapid conduction of electrical impulses in the heart. Cell adhesion molecules assist cardiac conduction by establishing specialised intercellular contacts that facilitate electrical coupling and mechanical contraction. In this study, Glenn Fishman and co-workers use RNAseq datasets to identify Alcam and Ncam-1 as highly enriched cell adhesion molecules in murine Purkinje cells. Both ALCAM and NCAM-1 are present in the developing heart, but become restricted to Purkinje cells by postnatal day 7. However, only a knockout of Ncam-1, but not Alcam or Cntn2 (another highly expressed cell adhesion gene in Purkinje cells), shows a slowing of ventricular conduction, which is accompanied by morphological defects in the left His-Purkinje system. Moreover, gene expression in Purkinje cells is altered upon Ncam-1 knockdown, which could contribute to perturbations in their electrophysiology. The authors further demonstrate that NCAM-1 is the primary target of polysialylation, a post-translation modification known to regulate NCAM-1 function, in the mouse heart. Polysialylation-deficient mice show aberrant targeting of sarcolemmal proteins in Purkinje cells and cardiac conduction defects. Together, these findings establish NCAM-1 as a novel factor involved in Purkinje cell function that could contribute to diseases associated with perturbations in cardiac conduction.
