Matrin-3-related distal myopathy is characterized mainly by progressive distal weakness of the lower extremities. The mutation p.S85C in matrin-3 (MATR3) has been identified as disease-causing alteration, whereas the specific molecular mechanisms leading to the muscle disease have not been elucidated. In the present study, muscle biopsy samples from six patients and fibroblasts from four patients harboring p.S85C mutation in MATR3 were analyzed. No specific changes in matrin-3 localization or expression were observed. In contrast, localization of the stress granule components G3BP1 and TIA1 was altered and enhanced protein- as well as RNA- expression of G3BP1 and TIA1 was observed in highly dystrophic tissues. Histological changes were pronounced in muscle biopsy specimen taken from distal muscles. In patient-derived primary fibroblasts, cellular response to oxidative stress was monitored using sodium arsenite treatment. The fraction of cells showing stress granule formation upon application of oxidative stress was significantly lower in patients' fibroblasts compared to healthy controls. Similar results were obtained for endoplasmatic reticulum stress using thapsigargin. Stress granule number in stress granule-positive cells with p.S85C mutation was significantly reduced, whereas stress granule size was not markedly altered. Consistently, cell viability upon arsenite treatment appeared significantly reduced in Matrin-3 myopathy derived fibroblasts. In summary, p.S85C mutation in matrin-3 affects the response to cellular stress by impairing stress granule formation and dynamics. This might contribute to cellular damage and progression of dystrophy in muscle of Matrin-3 myopathy.
Experimental Neurology – Elsevier
Published: Aug 1, 2018
It’s your single place to instantly
discover and read the research
that matters to you.
Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.
All for just $49/month
Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly
Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.
Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.
Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.
All the latest content is available, no embargo periods.
“Hi guys, I cannot tell you how much I love this resource. Incredible. I really believe you've hit the nail on the head with this site in regards to solving the research-purchase issue.”Daniel C.
“Whoa! It’s like Spotify but for academic articles.”@Phil_Robichaud
“I must say, @deepdyve is a fabulous solution to the independent researcher's problem of #access to #information.”@deepthiw
“My last article couldn't be possible without the platform @deepdyve that makes journal papers cheaper.”@JoseServera