title: The myotubularin-amphiphysin 2 complex in membrane tubulation and centronuclear myopathies.
abstract: 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.
authors.affiliation: 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.
authors.forename: Barbara
authors.initials: B
authors.lastname: Royer
authors.forename: Karim
authors.initials: K
authors.lastname: Hnia
authors.forename: Christos
authors.initials: C
authors.lastname: Gavriilidis
authors.forename: Hélène
authors.initials: H
authors.lastname: Tronchère
authors.forename: Valérie
authors.initials: V
authors.lastname: Tosch
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Laporte
mesh_terms: D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism*; D002522:Chlorocebus aethiops; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism; D020914:Myopathies, Structural, Congenital / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D011485:Protein Binding; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; C075637:amphiphysin; C089504:polyphosphoinositide phosphatase; D010744:Phosphoric Monoester Hydrolases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C099588:myotubularin
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