作者
Josine M De Winter, Joery P Molenaar, Michaela Yuen, Robbert Van Der Pijl, Shengyi Shen, Stefan Conijn, Martijn Van De Locht, Menne Willigenburg, Sylvia JP Bogaards, Esmee SB Van Kleef, Saskia Lassche, Malin Persson, Dilson E Rassier, Tamar E Sztal, Avnika A Ruparelia, Viola Oorschot, Georg Ramm, Thomas E Hall, Zherui Xiong, Christopher N Johnson, Frank Li, Balazs Kiss, Noelia Lozano-Vidal, Reinier A Boon, Manuela Marabita, Leonardo Nogara, Bert Blaauw, Richard J Rodenburg, Benno Küsters, Jonne Doorduin, Alan H Beggs, Henk Granzier, Ken Campbell, Weikang Ma, Thomas Irving, Edoardo Malfatti, Norma B Romero, Robert J Bryson-Richardson, Baziel GM Van Engelen, Nicol C Voermans, Coen AC Ottenheijm
发表日期
2020/2/18
期刊
The Journal of clinical investigation
卷号
130
期号
2
页码范围
754-767
出版商
American Society for Clinical Investigation
简介
The mechanisms that modulate the kinetics of muscle relaxation are critically important for muscle function. A prime example of the impact of impaired relaxation kinetics is nemaline myopathy caused by mutations in KBTBD13 (NEM6). In addition to weakness, NEM6 patients have slow muscle relaxation, compromising contractility and daily life activities. The role of KBTBD13 in muscle is unknown, and the pathomechanism underlying NEM6 is undetermined. A combination of transcranial magnetic stimulation–induced muscle relaxation, muscle fiber– and sarcomere-contractility assays, low-angle x-ray diffraction, and superresolution microscopy revealed that the impaired muscle-relaxation kinetics in NEM6 patients are caused by structural changes in the thin filament, a sarcomeric microstructure. Using homology modeling and binding and contractility assays with recombinant KBTBD13, Kbtbd13-knockout and …
学术搜索中的文章
JM De Winter, JP Molenaar, M Yuen, R Van Der Pijl… - The Journal of clinical investigation, 2020