| First Author | Staszewska I | Year | 2015 |
| Journal | Hum Mol Genet | Volume | 24 |
| Issue | 25 | Pages | 7373-89 |
| PubMed ID | 26487297 | Mgi Jnum | J:226972 |
| Mgi Id | MGI:5699472 | Doi | 10.1093/hmg/ddv438 |
| Citation | Staszewska I, et al. (2015) Plectin isoform 1-dependent nuclear docking of desmin networks affects myonuclear architecture and expression of mechanotransducers. Hum Mol Genet 24(25):7373-89 |
| abstractText | Plectin is a highly versatile cytoskeletal protein that acts as a mechanical linker between intermediate filament (IF) networks and various cellular structures. The protein is crucial for myofiber integrity. Its deficiency leads to severe pathological changes in skeletal muscle fibers of patients suffering from epidermolysis bullosa simplex with muscular dystrophy (EBS-MD). Skeletal muscle fibers express four major isoforms of plectin which are distinguished solely by alternative, relatively short, first exon-encoded N-terminal sequences. Each one of these isoforms is localized to a different subcellular compartment and plays a specific role in maintaining integrity and proper function(s) of myofibers. The unique role of individual isoforms is supported by distinct phenotypes of isoform-specific knockout mice and recently discovered mutations in first coding exons of plectin that lead to distinct, tissue-specific, pathological abnormalities in humans. In this study, we demonstrate that the lack of plectin isoform 1 (P1) in myofibers of mice leads to alterations of nuclear morphology, similar to those observed in various forms of MD. We show that P1-mediated targeting of desmin IFs to myonuclei is essential for maintenance of their typically spheroidal architecture as well as their proper positioning and movement along the myofiber. Furthermore, we show that P1 deficiency affects chromatin modifications and the expression of genes involved in various cellular functions, including signaling pathways mediating mechanotransduction. Mechanistically, P1 is shown to specifically interact with the myonuclear membrane-associated (BAR domain-containing) protein endophilin B. Our results open a new perspective on cytoskeleton-nuclear crosstalk via specific cytolinker proteins. |
