1] Department of Translational Medecine and Neurogenetics, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 1 Rue Laurent Fries 67404, [2] INSERM, U964, [3] CNRS, UMR7104, [4] Université de Strasbourg, [5] Collège de France, chaire de génétique humaine, Illkirch, France.
EMBO Rep. 2013 Oct;14(10):907-15. doi: 10.1038/embor.2013.119. Epub 2013 Aug 6.
Myotubularin (MTM1) and amphiphysin 2 (BIN1) are two proteins mutated in different forms of centronuclear myopathy, but the functional and pathological relationship between these two proteins was unknown. Here, we identified MTM1 as a novel binding partner of BIN1, both in vitro and endogenously in skeletal muscle. Moreover, MTM1 enhances BIN1-mediated membrane tubulation, depending on binding and phosphoinositide phosphatase activity. BIN1 patient mutations induce a conformational change in BIN1 and alter its binding and regulation by MTM1. In conclusion, we identified the first molecular and functional link between MTM1 and BIN1, supporting a common pathological mechanism in different forms of centronuclear myopathy.
肌小管素 1（MTM1）和 amphiphysin 2（BIN1）是两种在不同形式的中心核肌病中发生突变的蛋白质，但这两种蛋白质之间的功能和病理关系尚不清楚。在这里，我们鉴定出 MTM1 是 BIN1 的一个新的结合伴侣，无论是在体外还是在骨骼肌内源性地。此外，MTM1 增强了 BIN1 介导的膜管化，这取决于结合和磷酸肌醇磷酸酶活性。BIN1 患者突变诱导 BIN1 的构象变化，并改变其与 MTM1 的结合和调节。总之，我们确定了 MTM1 和 BIN1 之间的第一个分子和功能联系，支持了不同形式的中心核肌病中的共同病理机制。
