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Updated: Apr 21, 2026

Monitoring Cell-to-cell Transmission of Prion-like Protein Aggregates in Drosophila Melanogaster
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CryAB-driven amyloidogenesis in Drosophila muscle engages extracellular vesicle pathways for cellular release

Ziwei Zhao1, Hui-Ying Lim2, Elena Cannone3

  • 1Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, KS 66506, USA.

Iscience
|April 20, 2026
PubMed

Insights

Mutations in small heat shock protein alpha-crystallin B (CryAB) cause protein aggregation in muscle. This study reveals CryAB amyloid formation in skeletal muscle, suggesting new disease mechanisms.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Genetics

Background:

  • Mutations in alpha-crystallin B (CryAB) are linked to cataracts, cardiomyopathies, and myofibrillar myopathies (MFMs).
  • These diseases are characterized by the aggregation of proteins, including CryAB.
  • The pathological mechanisms underlying CryAB-related disorders are not fully understood.

Purpose of the Study:

  • To investigate the pathological mechanisms of CryAB mutations in skeletal muscle.
  • To determine if CryAB forms amyloid-like structures in muscle tissue.
  • To explore potential mechanisms of CryAB aggregate dissemination.

Main Methods:

  • Expressed four human CryAB disease alleles in Drosophila skeletal muscle.
  • Analyzed protein aggregation using thioflavin T spectroscopy and Congo red staining.
  • Examined colocalization with desmin, extracellular vesicle (EV) markers, and detected CryAB in hemolymph.

Main Results:

  • All expressed CryAB variants caused protein aggregate accumulation in Drosophila muscle.
  • Mutations in the alpha-crystallin domain (ACD) led to CryAB aggregates colocalizing with amyloidogenic desmin.
  • Amyloid-like CryAB structures were found to co-localize with EV markers and were present in hemolymph, suggesting EV-mediated export.

Conclusions:

  • This study demonstrates CryAB amyloid formation in skeletal muscle for the first time.
  • CryAB amyloidogenesis in muscle may contribute to myofibrillar myopathies and other related diseases.
  • Extracellular vesicle-mediated export is a potential mechanism for CryAB aggregate dissemination in muscle disorders.
Keywords:
Biological sciencesMolecular biologyNeuroscience

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