Drosophila Hsp67Bc hot-spot variants alter muscle structure and function

Cell Mol Life Sci. 2018 Dec;75(23):4341-4356. doi: 10.1007/s00018-018-2875-z. Epub 2018 Jul 21.


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.

Keywords: Development; Drosophila; Hsp67Bc; Muscle; Mutants; NMJ; Protein aggregates; sHSP.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Gene Expression
  • Heat-Shock Proteins / genetics*
  • Heat-Shock Proteins / metabolism
  • Larva / genetics
  • Larva / metabolism
  • Microscopy, Electron, Transmission
  • Motor Activity / genetics
  • Muscles / metabolism*
  • Mutation, Missense*
  • Neuromuscular Junction / metabolism*
  • Sarcoplasmic Reticulum / metabolism
  • Sarcoplasmic Reticulum / ultrastructure
  • Sequence Homology, Amino Acid


  • Drosophila Proteins
  • Heat-Shock Proteins
  • Hsp67Bc protein, Drosophila