| 2 | HACD1,a regulator of membrane composition and fluidity,promotes myoblast fusion and skeletal muscle growth显示文摘The reduced diameter of skeletal myofibres is a hallmark of several congenital myopathies,yet the underlying cellular and molecular mechanisms remain elusive.In this study,we investigate the role of HACD1/PTPLA,which is involved in the elongation of the very long chain fatty acids,in muscle fibre formation.In humans and dogs,HACD1 deficiency leads to a congenital myopathy with fibre size disproportion associated with a generalized muscleweakness.Throughanalysis of HACD1-deficient Labradors,Hacd1-knockout mice,and Hacd1-deficient myoblasts,we provide evidence that HACD1 promotes myoblast fusion during muscle development and regeneration.We further demonstrate that in normal differentiating myoblasts,expression of the catalytically active HACD1 isoform,which is encoded by a muscle-enriched splice variant,yields decreased lysophosphatidylcholine content,a potent inhibitor of myoblast fusion,and increased concentrations of≥C18 and monounsaturated fatty acids of phospholipids.These lipid modifications correlate with a reduction in plasma membrane rigidity.In conclusion,we propose that fusion impairment constitutes a novel,non-exclusive pathological mechanism operating in congenital myopathies and reveal that HACD1 is a key regulator of a lipid-dependent muscle fibre growth mechanism. | Jordan Blondelle Yusuke Ohno Vincent Gache Stephane Guyot Sebastien Storck Nicolas Blanchard-Gutton Ines Barthelemy Gemma Walmsley Anaelle Rahier Stephanie Gadin Marie Maurer Laurent Guillaud Alexandre Prola Arnaud Ferry Genevieve Aubin-Houzelstein Jean Demarquoy Frederic Relaix Richard JPiercy Stephane Blot Akio Kihara Laurent Tiret Fanny Pilot-Storck | 2015 | Journal of Molecular Cell Biology2015，7，5： | 1 |
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