Primary T-tubule and autophagy defects in the phosphoinositide phosphatase Jumpy/MTMR14 knockout mice muscle Karim Hnia a, b, c, d, e , Christine Kretz a, b, c, d, e , Leonela Amoasii a, b, c, d, e , Johann Böhm a, b, c, d, e , Xia Liu f , Nadia Messaddeq a, b, c, d , Cheng-Kui Qu f , Jocelyn Laporte a, b, c, d, e, * a Department of Translational Medicine and Neurogenetics, IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), 1, rue Laurent Fries, BP10142, 67404 Illkirch, France b U964, Institut National de la Santé et de la Recherche Médicale, Illkirch, France c UMR7104, Centre National de la Recherche Scientifique, Illkirch, France d Université de Strasbourg, France e Chaire de Génétique Humaine, Collège de France, Illkirch, France f Department of Medicine, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA Introduction Muscle fibers can efficiently contract to promote body movement and are site of energy storage. These important properties are sustained by their intricate intracellular structure. In particular, membrane remodelling and trafficking play a central role in these processes. The phosphoinositides (PIs) second messengers are key regulator of intramembrane organization and dynamics. However, the roles of phosphoinositides and membrane organization in muscle functions under normal and path- ological conditions are not well defined. Two families of PI-phosphatases have been implicated in myopathies: myotubularins and Jumpy/ MTMR14 (Lecompte et al., 2008). Human myotubularins (MTM1 and MTMR1-13) are phosphoinositide 3-phosphatases or phosphatase-like proteins mutated in several neuromuscular disorders (Laporte et al., 2003; Previtali et al., 2007; Taylor and Dixon, 2003; Wishart and Dixon, 2002). MTM1 is mutated in X-linked myotubular (centronuclear) myopathy (XLMTM) (Laporte et al., 1996), whereas MTMR2 and MTMR13 are mutated in demyelinating Charcot–Marie–Tooth neuropathy types 4B1 and 4B2, respectively (Azzedine et al., 2003; Bolino et al., 2000; Senderek et al., 2003). Myotubularins share homology to the catalytic domains of protein tyrosine phosphatases and dual-specificity phosphatases * Corresponding author. Department of Translational Medicine and Neurogenetics, IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire),1, rue Laurent Fries, BP10142, 67404 Illkirch, France. Tel.: þ33 388653412. E-mail address: jocelyn@igbmc.fr (J. Laporte). Contents lists available at SciVerse ScienceDirect Advances in Enzyme Regulation journal homepage: www.elsevier.com/locate/ advenzreg 0065-2571/$ – see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.advenzreg.2011.09.007 Advances in Enzyme Regulation 52 (2012) 98–107