Myotubularin and PtdIns3P remodel the sarcoplasmic reticulum in muscle in vivo

被引:56
作者
Amoasii, Leonela [1 ]
Hnia, Karim [1 ]
Chicanne, Gaetan [2 ,3 ]
Brech, Andreas [4 ]
Cowling, Belinda S. [1 ]
Mueller, Martin Michael [5 ]
Schwab, Yannick [1 ]
Koebel, Pascale [1 ]
Ferry, Arnaud [6 ]
Payrastre, Bernard [2 ,3 ,7 ]
Laporte, Jocelyn [1 ]
机构
[1] Univ Strasbourg, Coll France, Inst Genet & Biol Mol & Cellulaire, Dept Translat Med,INSERM U964,CNRS UMR7104, F-67404 Illkirch Graffenstaden, France
[2] INSERM, U1048, F-31432 Toulouse 04, France
[3] Univ Toulouse 3, I2MC, F-31432 Toulouse 04, France
[4] Norwegian Radium Hosp, Inst Canc Res, Dept Biochem, N-0310 Oslo, Norway
[5] Univ Lorraine, ICPMB FR CNRS 2843, Equipe BioPhysStat, F-57070 Metz, France
[6] Univ Paris 06, UMRS974, Paris, France
[7] CHU Toulouse, Hematol Lab, F-31059 Toulouse 04, France
关键词
MTM1; PtdIns3P; Sarcoplasmic reticulum; Membrane remodeling; PI3P; CELL-MEMBRANE ORGANIZATION; RABBIT SKELETAL-MUSCLE; PHOSPHATIDYLINOSITOL; 3-PHOSPHATE; TRANSVERSE TUBULES; ENDOPLASMIC-RETICULUM; CUBIC MEMBRANES; BIOCHEMICAL-PROPERTIES; SUBSTRATE-SPECIFICITY; MAMMALIAN-CELLS; EARLY ENDOSOMES;
D O I
10.1242/jcs.118505
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The sarcoplasmic reticulum (SR) is a specialized form of endoplasmic reticulum (ER) in skeletal muscle and is essential for calcium homeostasis. The mechanisms involved in SR remodeling and maintenance of SR subdomains are elusive. In this study, we identified myotubularin (MTM1), a phosphoinositide phosphatase mutated in X-linked centronuclear myopathy (XLCNM, or myotubular myopathy), as a key regulator of phosphatidylinositol 3-monophosphate (PtdIns3P) levels at the SR. MTM1 is predominantly located at the SR cisternae of the muscle triads, and Mtm1-deficient mouse muscles and myoblasts from XLCNM patients exhibit abnormal SR/ER networks. In vivo modulation of MTM1 enzymatic activity in skeletal muscle using ectopic expression of wild-type or a dead-phosphatase MTM1 protein leads to differential SR remodeling. Active MTM1 is associated with flat membrane stacks, whereas dead-phosphatase MTM1 mutant promotes highly curved cubic membranes originating from the SR and enriched in PtdIns3P. Overexpression of a tandem FYVE domain with high affinity for PtdIns3P alters the shape of the SR cisternae at the triad. Our findings, supported by the parallel analysis of the Mtm1-null mouse and an in vivo study, reveal a direct function of MTM1 enzymatic activity in SR remodeling and a key role for PtdIns3P in promoting SR membrane curvature in skeletal muscle. We propose that alteration in SR remodeling is a primary cause of X-linked centronuclear myopathy. The tight regulation of PtdIns3P on specific membrane subdomains may be a general mechanism to control membrane curvature.
引用
收藏
页码:1806 / 1819
页数:14
相关论文
共 67 条
[61]   Congenital muscle disorders with cores: the ryanodine receptor calcium channel paradigm [J].
Treves, Susan ;
Jungbluth, Heinz ;
Muntoni, Francesco ;
Zorzato, Francesco .
CURRENT OPINION IN PHARMACOLOGY, 2008, 8 (03) :319-326
[62]   Production of phosphatidylinositol 5-phosphate by the phosphoinositide 3-phosphatase myotubularin in mammalian cells [J].
Tronchère, H ;
Laporte, J ;
Pendaries, C ;
Chaussade, C ;
Liaubet, L ;
Pirola, L ;
Mandel, JL ;
Payrastre, B .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (08) :7304-7312
[63]   Myotubularin regulates the function of the late endosome through the GRAM domain-phosphatidylinositol 3,5-bisphosphate interaction [J].
Tsujita, K ;
Itoh, T ;
Ijuin, T ;
Yamamoto, A ;
Shisheva, A ;
Laporte, J ;
Takenawa, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (14) :13817-13824
[64]   INVESTIGATIONS ON FINE STRUCTURE OF STRIATED MUSCLE FIBER [J].
VERATTI, E .
JOURNAL OF BIOPHYSICAL AND BIOCHEMICAL CYTOLOGY, 1961, 10 :1-&
[65]  
Yamamoto A, 1996, J CELL SCI, V109, P1727
[66]  
Zorzano A., 2006, CURR PROTOC CELL BIO, V31
[67]   Myotubularin-related protein (MTMR) 9 determines the enzymatic activity, substrate specificity, and role in autophagy of MTMR8 [J].
Zou, Jun ;
Zhang, Chunfen ;
Marjanovic, Jasna ;
Kisseleva, Marina V. ;
Majerus, Philip W. ;
Wilson, Monita P. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (24) :9539-9544