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Studying Proteolysis of Cyclin B at the Single Cell Level in Whole Cell Populations
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Published on: September 17, 2012

A splice variant of cyclin D2 regulates cardiomyocyte cell cycle through a novel protein aggregation pathway

Qian Sun1, Feixiong Zhang, Karim Wafa

  • 1Department of Pharmacology, Sir Charles Tupper Medical Building, Dalhousie University, Halifax, NS, B3H 1X5 Canada.

Journal of Cell Science
|April 30, 2009
PubMed

Insights

A novel protein variant, cyclin D2 splice variant (D2SV), identified in mouse hearts, halts cardiomyocyte cell division. This discovery offers insights into preventing heart muscle regeneration by understanding cell cycle exit mechanisms.

Area of Science:

  • Cardiovascular Biology
  • Cell Cycle Regulation
  • Molecular Cardiology

Background:

  • Mammalian hearts have limited capacity for myocyte regeneration.
  • Mechanisms controlling cardiomyocyte cell cycle exit are poorly understood.

Purpose of the Study:

  • To investigate the role of a novel cyclin D2 splice variant (D2SV) in cardiomyocyte cell cycle exit.
  • To elucidate the molecular mechanisms underlying D2SV function in heart development and regeneration.

Main Methods:

  • Cloning and characterization of mouse D2SV.
  • Immunofluorescence and subcellular localization studies.
  • Analysis of protein-protein interactions and aggregation.
  • Manipulation of D2SV expression and cell cycle activity in cardiomyocytes.

Main Results:

  • D2SV is highly expressed in embryonic myocardium and decreases in adult hearts.
  • D2SV localizes to the endoplasmic reticulum, Golgi, and lysosomes, undergoing ER-stress-associated aggregation.
  • D2SV aggregation is dependent on dynein motor activity and modulated by ER stress.
  • D2SV sequesters other cell cycle proteins, promoting cell cycle exit.
  • Overexpression of D-type and B-type cyclins can rescue D2SV-induced cell cycle arrest.

Conclusions:

  • D2SV plays a critical role in cardiomyocyte cell cycle exit during development.
  • Protein aggregation of D2SV may represent a significant barrier to cardiomyocyte cell cycle reactivation and heart repair.

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