Primary T-tubule and autophagy defects in the phosphoinositide phosphatase Jumpy/MTMR14 knockout mice muscle

Abstract

IntroductionMuscle 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)secondmessengersarekeyregulatorofintramembraneorganizationanddynamics.However,theroles 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 etal.,2008).Humanmyotubularins(MTM1andMTMR1-13)arephosphoinositide3-phosphatases or phosphatase-like proteins mutated in several neuromuscular disorders (Laporteet al., 2003; Previtali et al., 2007; Taylor and Dixon, 2003; Wishart and Dixon, 2002). MTM1 ismutated in X-linked myotubular (centronuclear) myopathy (XLMTM) (Laporte et al., 1996), whereasMTMR2 and MTMR13 are mutated in demyelinating Charcot–Marie–Tooth neuropathy types 4B1 and4B2,respectively(Azzedineetal.,2003;Bolinoetal.,2000;Sendereketal.,2003).Myotubularinssharehomology tothe catalytic domainsof protein tyrosine phosphatases and dual-specificity phosphatases