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Target formation in muscle fibres indicates reinnervation -- A proteomic study in muscle samples from peripheral neuropathies.
- Source :
-
Neuropathology & Applied Neurobiology . Feb2023, Vol. 49 Issue 1, p1-15. 15p. - Publication Year :
- 2023
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Abstract
- Aims: Target skeletal muscle fibres - defined by different concentric areas in oxidative enzyme staining - can occur in patients with neurogenic muscular atrophy. Here, we used our established hypothesis-free proteomic approach with the aim of deciphering the protein composition of targets. We also searched for potential novel interactions between target proteins. Methods: Targets and control areas were laser microdissected from skeletal muscle sections of 20 patients with neurogenic muscular atrophy. Samples were analysed by a highly sensitive mass spectrometry approach, enabling relative protein quantification. The results were validated by immunofluorescence studies. Protein interactions were investigated by yeast two-hybrid assays, coimmunoprecipitation experiments and bimolecular fluorescence complementation. Results: More than 1000 proteins were identified. Among these, 55 proteins were significantly over-represented and 40 proteins were significantly under-represented in targets compared to intraindividual control samples. The majority of over-represented proteins were associated with the myofibrillar Z-disc and actin dynamics, followed by myosin and myosin-associated proteins, proteins involved in protein biosynthesis and chaperones. Under-represented proteins were mainly mitochondrial proteins. Functional studies revealed that the LIM domain of the over-represented protein LIMCH1 interacts with isoform A of Xin actin-binding repeat-containing protein 1 (XinA). Conclusions: In particular, proteins involved in myofibrillogenesis are over-represented in target structures, which indicate an ongoing process of sarcomere assembly and/or remodelling within this specific area of the muscle fibres. We speculate that target structures are the result of reinnervation processes in which filamin C-associated myofibrillo-genesis is tightly regulated by the BAG3-associated protein quality system. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03051846
- Volume :
- 49
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Neuropathology & Applied Neurobiology
- Publication Type :
- Academic Journal
- Accession number :
- 161733537
- Full Text :
- https://doi.org/10.1111/nan.12853