Neural cell adhesion molecule is required for ventricular conduction system development. Academic Article uri icon

Overview

abstract

  • The most distal portion of the ventricular conduction system (VCS) contains cardiac Purkinje cells (PCs), which are essential for synchronous activation of the ventricular myocardium. Contactin-2 (CNTN2), a member of the immunoglobulin superfamily of cell adhesion molecules (IgSF-CAMs), was previously identified as a marker of the VCS. Through differential transcriptional profiling, we discovered two additional highly enriched IgSF-CAMs in the VCS: NCAM-1 and ALCAM. Immunofluorescence staining showed dynamic expression patterns for each IgSF-CAM during embryonic and early postnatal stages, but ultimately all three proteins became highly enriched in mature PCs. Mice deficient in NCAM-1, but not CNTN2 or ALCAM, exhibited defects in PC gene expression and VCS patterning, as well as cardiac conduction disease. Moreover, using ST8sia2 and ST8sia4 knockout mice, we show that inhibition of post-translational modification of NCAM-1 by polysialic acid leads to disrupted trafficking of sarcolemmal intercalated disc proteins to junctional membranes and abnormal expansion of the extracellular space between apposing PCs. Taken together, our data provide insights into the complex developmental biology of the ventricular conduction system.

publication date

  • June 7, 2021

Research

keywords

  • Heart Ventricles
  • Neural Cell Adhesion Molecules
  • Neurogenesis

Identity

PubMed Central ID

  • PMC8217711

Scopus Document Identifier

  • 85107875620

Digital Object Identifier (DOI)

  • 10.1046/j.1471-4159.1994.62031231.x

PubMed ID

  • 34100064

Additional Document Info

volume

  • 148

issue

  • 11