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Islam M, Diwan A, Mani K. Come Together: Protein Assemblies, Aggregates and the Sarcostat at the Heart of Cardiac Myocyte Homeostasis. Front Physiol. 2020;11:586doi: 10.3389/fphys.2020.00586.
Islam, M., Diwan, A., & Mani, K. (2020). Come Together: Protein Assemblies, Aggregates and the Sarcostat at the Heart of Cardiac Myocyte Homeostasis. Frontiers in physiology, 11586. https://doi.org/10.3389/fphys.2020.00586
Islam, Moydul, et al. "Come Together: Protein Assemblies, Aggregates and the Sarcostat at the Heart of Cardiac Myocyte Homeostasis." Frontiers in physiology vol. 11 (2020): 586. doi: https://doi.org/10.3389/fphys.2020.00586
Islam M, Diwan A, Mani K. Come Together: Protein Assemblies, Aggregates and the Sarcostat at the Heart of Cardiac Myocyte Homeostasis. Front Physiol. 2020 Jun 04;11:586. doi: 10.3389/fphys.2020.00586. eCollection 2020. PMID: 32581848; PMCID: PMC7287178.
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Front Physiol. 2020 Jun 04;11:586. doi: 10.3389/fphys.2020.00586. eCollection 2020.

Come Together: Protein Assemblies, Aggregates and the Sarcostat at the Heart of Cardiac Myocyte Homeostasis.

Frontiers in physiology

Moydul Islam, Abhinav Diwan, Kartik Mani

Affiliations

  1. Division of Cardiology, Washington University School of Medicine, St. Louis, MO, United States.
  2. Center for Cardiovascular Research, Washington University School of Medicine, St. Louis, MO, United States.
  3. Department of Chemistry, Washington University in St. Louis, St. Louis, MO, United States.
  4. John Cochran Veterans Affairs Medical Center, St. Louis, MO, United States.

PMID: 32581848 PMCID: PMC7287178 DOI: 10.3389/fphys.2020.00586

Abstract

Homeostasis in vertebrate systems is contingent on normal cardiac function. This, in turn, depends on intricate protein-based cellular machinery, both for contractile function, as well as, durability of cardiac myocytes. The cardiac small heat shock protein (csHsp) chaperone system, highlighted by αB-crystallin (CRYAB), a small heat shock protein (sHsp) that forms ∼3-5% of total cardiac mass, plays critical roles in maintaining proteostatic function via formation of self-assembled multimeric chaperones. In this work, we review these ancient proteins, from the evolutionarily preserved role of homologs in protists, fungi and invertebrate systems, as well as, the role of sHsps and chaperones in maintaining cardiac myocyte structure and function. We propose the concept of the "sarcostat" as a protein quality control mechanism in the sarcomere. The roles of the proteasomal and lysosomal proteostatic network, as well as, the roles of the aggresome, self-assembling protein complexes and protein aggregation are discussed in the context of cardiac myocyte homeostasis. Finally, we will review the potential for targeting the csHsp system as a novel therapeutic approach to prevent and treat cardiomyopathy and heart failure.

Copyright © 2020 Islam, Diwan and Mani.

Keywords: aggregates; autophagy; heat shock proteins; lysosome; ubiquitin 26S-proteasome system

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