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Updated: May 31, 2026
Monitoring Cell-to-cell Transmission of Prion-like Protein Aggregates in Drosophila Melanogaster
Published on: March 12, 2018
Drosophila melanogaster as a model system for studies of islet amyloid polypeptide aggregation
Sebastian Wolfgang Schultz1, K Peter R Nilsson, Gunilla Torstensdotter Westermark
1Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Background:
Recent research supports that aggregation of islet amyloid polypeptide (IAPP) leads to cell death and this makes islet amyloid a plausible cause for the reduction of beta cell mass, demonstrated in patients with type 2 diabetes. IAPP is produced by the beta cells as a prohormone, and proIAPP is processed into IAPP by the prohormone convertases PC1/3 and PC2 in the secretory granules. Little is known about the pathogenesis for islet amyloid and which intracellular mechanisms are involved in amyloidogenesis and induction of cell death.
Methodology/Principal Findings:
We have established expression of human proIAPP (hproIAPP), human IAPP (hIAPP) and the non-amyloidogenic mouse IAPP (mIAPP) in Drosophila melanogaster, and compared survival of flies with the expression driven to different cell populations. Only flies expressing hproIAPP in neurons driven by the Gal4 driver elav(C155,Gal4) showed a reduction in lifespan whereas neither expression of hIAPP or mIAPP influenced survival. Both hIAPP and hproIAPP expression caused formation of aggregates in CNS and fat body region, and these aggregates were both stained by the dyes Congo red and pFTAA, both known to detect amyloid. Also, the morphology of the highly organized protein granules that developed in the fat body of the head in hIAPP and hproIAPP expressing flies was characterized, and determined to consist of 15.8 nm thick pentagonal rod-like structures.
Conclusions/Significance:
These findings point to a potential for Drosophila melanogaster to serve as a model system for studies of hproIAPP and hIAPP expression with subsequent aggregation and developed pathology.
Insights
The expression of human islet amyloid polypeptide precursor (hproIAPP) in fruit fly neurons reduces lifespan and forms amyloid aggregates. This suggests Drosophila melanogaster is a valuable model for studying IAPP-related diseases like type 2 diabetes.
Area of Science:
- Biochemistry
- Cell Biology
- Neuroscience
Background:
- Islet amyloid polypeptide (IAPP) aggregation is linked to beta cell death and type 2 diabetes.
- The intracellular mechanisms driving islet amyloidogenesis and cell death remain poorly understood.
Purpose of the Study:
- To investigate the role of human proIAPP (hproIAPP) and human IAPP (hIAPP) in amyloid formation and pathology.
- To establish Drosophila melanogaster as a model system for studying IAPP-related diseases.
Main Methods:
- Expressed hproIAPP, hIAPP, and mouse IAPP (mIAPP) in Drosophila melanogaster.
- Drove expression in specific cell populations using the Gal4 driver elav(C155,Gal4).
- Analyzed fly lifespan, aggregate formation (using Congo red and pFTAA staining), and aggregate morphology.
Main Results:
- Expression of hproIAPP in neurons significantly reduced fly lifespan.
- Neither hIAPP nor mIAPP expression affected fly survival.
- Both hIAPP and hproIAPP formed amyloid aggregates in the central nervous system and fat body.
- Aggregates consisted of 15.8 nm thick pentagonal rod-like structures.
Conclusions:
- Drosophila melanogaster serves as a viable model for studying hproIAPP and hIAPP aggregation and associated pathology.
- Findings highlight the potential neurotoxic effects of hproIAPP.
