Small heat-shock proteins and their role in mechanical stress

Abstract

The ability of cells to respond to stress is central to health. Stress can damage folded proteins, which are vulnerable to even minor changes in cellular conditions. To maintain proteostasis, cells have developed an intricate network in which molecular chaperones are key players. The small heat-shock proteins (sHSPs) are a widespread family of molecular chaperones, and some sHSPs are prominent in muscle, where cells and proteins must withstand high levels of applied force. sHSPs have long been thought to act as general interceptors of protein aggregation. However, evidence is accumulating that points to a more specific role for sHSPs in protecting proteins from mechanical stress. Here, we briefly introduce the sHSPs and outline the evidence for their role in responses to mechanical stress. We suggest that sHSPs interact with mechanosensitive proteins to regulate physiological extension and contraction cycles. It is likely that further study of these interactionsenabled by the development of experimental methodologies that allow protein contacts to be studied under the application of mechanical forcewill expand our understanding of the activity and functions of sHSPs, and of the roles played by chaperones in general.

Homozygous expression of the myofibrillar myopathy-associated p.W2710X filamin C variant reveals major pathomechanisms of sarcomeric lesion formation

“…Accordingly, interference with HSPB7 expression in zebrafish and human cardiomyocytes also results in increased load by damaged proteins and stimulation of autophagic pathways [ 50 ]. Further studies are necessary to resolve the cause for its strongly reduced expression in our Hom mice, and to elucidate its precise role, both in actin-based assembly and regulation of autophagic pathways [ 13 ].…”

Genetics of Peripartum Cardiomyopathy: Current Knowledge, Future Directions and Clinical Implications

“…Included in the Hsp family are small heat shock proteins (sHsps), which are ubiquitously expressed regulators of cellular protein folding [ 30 ]. The high expression of sHsps in the heart has been reported, where they are implicated in the maintenance of normal cardiac function and regulation of the cardiac stress response [ 50 , 51 ].…”

Real time observation of chaperone-modulated talin mechanics with single molecule resolution

“…13 Studies have shown that chaperones like α β crystallin or calreticulin has played crucial role in deciding mechanical properties of cell, like resilience of cell adhesion, cell spreading, by regulating expression of key focal adhesion proteins. 13,14 Small heat shock proteins have also been observed to regulate chronic biomechanical stress in heart tissue by regulating dynamics of key FA protein like actin and filamin C. 17 Additionally, tension-induced ubiquitylation of filamin A promotes chaperone-assisted autophagy which in turn dictate the role of chaperones in focal adhesion assembly. 35,36 However, the underlying molecular mechanism of these chaperone interactions, during mechanotransduction, has not been reported yet.…”