WANTED - Dead or alive: Myotubularins, a large disease-associated protein family

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• 作者：Matthieu A. Raess^a ; ^b ; ^c ; ^d ; ^e ; ^{raess@igbmc.fr} ; Sylvie Friant^e ; ^{s.friant@unistra.fr} ; Belinda S. Cowling^a ; ^b ; ^c ; ^d ; ^{belinda@igbmc.fr} ; Jocelyn Laporte^a ; ^b ; ^c ; ^d ; ^{jocelyn@igbmc.fr}
• 关键词：Congenital myopathy ; Neuropathy ; GTEx database ; Sbf1 ; Myotubular myopathy ; Myotubularin
• 刊名：Advances in Biological Regulation
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：63
• 期：Complete
• 页码：49-58
• 全文大小：2019 K
• 卷排序：63

文摘

Myotubularins define a large family of proteins conserved through evolution. Several members are mutated in different neuromuscular diseases including centronuclear myopathies and Charcot-Marie-Tooth (CMT) neuropathies, or are linked to a predisposition to obesity and cancer. While some members have phosphatase activity against the 3-phosphate of phosphoinositides, regulating the phosphorylation status of PtdIns3P and PtdIns(3,5)P2 implicated in membrane trafficking and autophagy, and producing PtdIns5P, others lack key residues in the catalytic site and are classified as dead-phosphatases. However, these dead phosphatases regulate phosphoinositide-dependent cellular pathways by binding to catalytically active myotubularins. Here we review previous studies on the molecular regulation and physiological roles of myotubularins. We also used the recent myotubularins three-dimensional structures to underline key residues that are mutated in neuromuscular diseases and required for enzymatic activity. In addition, through database mining and analysis, expression profile and specific isoforms of the different myotubularins are described in depth, as well as a revisited protein interaction network. Comparison of the interactome and expression data for each myotubularin highlights specific protein complexes and tissues where myotubularins should have a key regulatory role.