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Purification of Transcripts and Metabolites from Drosophila Heads
Published on: March 15, 2013
Proteomic analysis of a drosophila IBMPFD model reveals potential pathogenic mechanisms
Hsin-Tzu Chan1, Tian-Ren Lee, Shun-Hong Huang
1Institute of Bioinformatics and Structural Biology & Department of Medical Sciences, National Tsing Hua University, Hsinchu, Taiwan.
Abstract:
IBMPFD, Inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia, is a hereditary degenerative disorder due to single missense mutations in VCP (Valosin-Containing Protein). The mechanisms of how mutations of VCP lead to IBMPFD remain mysterious. Here we utilize two-dimensional difference gel electrophoresis (2D-DIGE) combined with mass spectrometry to study the IBMPFD disorder at the protein level. With this set-up, we are able to employ comparative proteomics to analyze IBMPFD disease using Drosophila melanogaster as our disease model organism. Head proteome of transgenic D. melanogaster expressing wild type VCP is compared, respectively, with the head proteome of transgenic mutant type VCPs that correspond to human IBMPFD disease alleles (TER94(A229E), TER94(R188Q), and TER94(R152H)). Of all the proteins identified, a significant fraction of proteins altered in TER94(A229E) and TER94(R188Q) mutants belong to the same functional categories, i.e. apoptosis and metabolism. Among these, Drosophila transferrin is observed to be significantly up-regulated in mutant flies expressing TER94(A229E). A knock-down experiment suggests that fly transferrin might be a potential modifier in IBMPFD disease. The molecular analysis of IBMPFD disease may benefit from the proteomics approach which combines the advantages of high throughput analysis and the focus on protein levels.
Insights
Inclusion body myopathy with Paget's disease and frontotemporal dementia (IBMPFD) is linked to VCP gene mutations. Proteomics in Drosophila revealed altered apoptosis and metabolism proteins, suggesting transferrin as a potential disease modifier.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Inclusion body myopathy with Paget's disease and frontotemporal dementia (IBMPFD) is a rare genetic disorder.
- The underlying molecular mechanisms of IBMPFD, caused by mutations in the Valosin-Containing Protein (VCP) gene, are not well understood.
Purpose of the Study:
- To investigate the protein level changes associated with IBMPFD using a Drosophila melanogaster model.
- To identify potential protein modifiers of IBMPFD.
Main Methods:
- Comparative proteomics using two-dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry.
- Analysis of head proteomes from transgenic Drosophila expressing wild-type and mutant VCP (TER94(A229E), TER94(R188Q), TER94(R152H)).
Main Results:
- Proteins involved in apoptosis and metabolism were significantly altered in TER94(A229E) and TER94(R188Q) mutants.
- Drosophila transferrin showed significant upregulation in the TER94(A229E) mutant.
- Knock-down experiments indicated transferrin as a potential modifier of IBMPFD.
Conclusions:
- Proteomics is a valuable approach for studying IBMPFD, offering high-throughput analysis at the protein level.
- Drosophila transferrin emerges as a potential therapeutic target or modifier for IBMPFD.
