Abstract
The Drosophila Hsp67Bc gene encodes a protein belonging to the small heat-shock protein (sHSP) family, identified as the nearest functional ortholog of human HSPB8. The most prominent activity of sHSPs is preventing the irreversible aggregation of various non-native polypeptides. Moreover, they are involved in processes such as development, aging, maintenance of the cytoskeletal architecture and autophagy. In larval muscles Hsp67Bc localizes to the Z- and A-bands, which suggests its role as part of the conserved chaperone complex required for Z-disk maintenance. In addition, Hsp67Bc is present at neuromuscular junctions (NMJs), which implies its involvement in the maintenance of NMJ structure. Here, we report the effects of muscle-target overexpression of Drosophila Hsp67Bc hot-spot variants Hsp67BcR126E and Hsp67BcR126N mimicking pathogenic variants of human HSPB8. Depending on the substitutions, we observed a different impact on muscle structure and performance. Expression of Hsp67BcR126E affects larval motility, which may be caused by impairment of mitochondrial respiratory function and/or by NMJ abnormalities manifested by a decrease in the number of synaptic boutons. In contrast, Hsp67BcR126N appears to be an aggregate-prone variant, as reflected in excessive accumulation of mutant proteins and the formation of large aggregates with a lesser impact on muscle structure and performance compared to the Hsp67BcR126E variant.
Highlights
Small heat-shock proteins constitute an evolutionarily conserved group of low molecular weight ubiquitous proteins present in almost all organisms [38]
The Drosophila Hsp67Bc protein belongs to the family of small heat-shock proteins and is thought to be the functional ortholog of vertebrate HSPB8 (Fig. 1) [8]
The protein contains a conserved alpha-crystallin domain (ACD) comprising an immunoglobulin-like fold, which plays an important role in small heat-shock protein (sHSP) assembly
Summary
Small heat-shock proteins (sHSPs; HSPB) constitute an evolutionarily conserved group of low molecular weight (ranging from 10 to 40 kDa) ubiquitous proteins present in almost all organisms [38]. The sHSPs are involved in the response to stress conditions such as heat or oxidative stress. Their most prominent activity is preventing, in an ATP-independent manner, the irreversible aggregation of various non-native proteins, and the formation of potentially pathogenic aggregates. Through these activities, sHSPs are involved in development, aging, regulation of apoptosis, maintenance of the cytoskeleton architecture, and autophagy [15, 51]
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