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Immunoglobulin-like Cell Adhesion Molecules01:31

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Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
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The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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The cardiac conduction system produces and transmits electrical impulses that prompt myocardial contraction, ensuring efficient heart function. This intricate system ensures that the heart beats in a coordinated and efficient manner, beginning with the atria and then the ventricles. The conduction system optimizes cardiac output by maintaining this precise sequence, which is crucial for adequate blood circulation.
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Neural cell adhesion molecule is required for ventricular conduction system development.

Camila Delgado1, Lei Bu1, Jie Zhang1

  • 1Leon H. Charney Division of Cardiology, Department of Medicine, NYU Grossman School of Medicine, NY 10016, USA.

Development (Cambridge, England)
|June 8, 2021
PubMed
Summary
This summary is machine-generated.

Neural cell adhesion molecules (NCAMs) like NCAM-1 are crucial for cardiac Purkinje cell development and ventricular conduction system patterning. NCAM-1 deficiency causes cardiac conduction disease and disrupted cell-cell interactions.

Keywords:
Cardiac conduction systemCell adhesion moleculeMouseNCAM-1Polysialic acidPurkinje cellVentricular conduction system

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Area of Science:

  • Cardiovascular Biology
  • Developmental Neuroscience
  • Molecular Cell Biology

Background:

  • The ventricular conduction system (VCS) relies on cardiac Purkinje cells (PCs) for efficient electrical signal propagation.
  • Immunoglobulin superfamily cell adhesion molecules (IgSF-CAMs) are implicated in neural development, but their role in VCS development is less understood.
  • Contactin-2 (CNTN2) was previously identified as a marker of the VCS.

Purpose of the Study:

  • To identify novel IgSF-CAMs expressed in the VCS.
  • To investigate the role of identified IgSF-CAMs in PC development and VCS formation.
  • To elucidate the functional impact of NCAM-1 and its post-translational modifications on cardiac conduction.

Main Methods:

  • Differential transcriptional profiling of VCS.
  • Immunofluorescence staining for IgSF-CAMs during embryonic and postnatal development.
  • Analysis of knockout mouse models (NCAM-1, CNTN2, ALCAM, ST8sia2, ST8sia4).
  • Assessment of cardiac gene expression, VCS patterning, and protein trafficking.

Main Results:

  • NCAM-1 and ALCAM were identified as novel IgSF-CAMs highly enriched in the VCS.
  • Mice deficient in NCAM-1 displayed impaired PC gene expression, VCS patterning, and cardiac conduction disease.
  • Loss of polysialic acid modification on NCAM-1 disrupted protein trafficking and widened the space between PCs.

Conclusions:

  • NCAM-1 is essential for the proper development and function of the ventricular conduction system.
  • Post-translational modification of NCAM-1 by polysialic acid is critical for maintaining PC structure and function.
  • These findings reveal novel molecular mechanisms governing VCS development and cardiac conduction.