Trim32 is a ubiquitin ligase mutated in limb girdle muscular dystrophy type 2H that binds to skeletal muscle myosin and ubiquitinates actin

被引:158
作者
Kudryashova, E
Kudryashov, D
Kramerova, I
Spencer, MJ [1 ]
机构
[1] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Dept Pediat, Duchenne Muscular Dystrophy Res Ctr, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA
关键词
E3 ubiquitin ligase; skeletal muscle; LGMD2H; tripartite motif family; myofibrillar proteins;
D O I
10.1016/j.jmb.2005.09.068
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Trim32 belongs to the tripartite motif (TRIM) protein family, which is characterized by a common domain structure composed of a RING-finger, a B-box, and a coiled-coil motif. In addition to these motifs, Trim32 possesses six C-terminal NHL-domains. A point mutation in one NHL domain (D487N) has been linked to two forms of muscular dystrophy called limb girdle muscular dystrophy type 2H and sarcotubular myopathy. In the present study we demonstrate that Trim32 is an E3 ubiquitin ligase that acts in conjunction with ubiquitin-conjugating enzymes UbcH5a, UbcH5c, and UbcH6. Western blot analysis showed that Trim32 is expressed primarily in skeletal muscle, and revealed its differential expression from one muscle to another. The level of Trim32 expression was elevated significantly in muscle undergoing remodeling due to changes in weight bearing. Furthermore, expression of Trim32 was induced in myogenic differentiation. Thus, variability in Trim32 expression in different skeletal muscles could be due to induction of Trim32 expression upon changes in physiological conditions. We show that Trim32 associates with skeletal muscle thick filaments, interacting directly with the head and neck region of myosin. Our data indicate that myosin is not a substrate of Trim32; however, Trim32 was found to ubiquitinate actin in vitro and to cause a decrease in the level of endogenous actin when transfected into HEK293 cells. In conclusion, our results demonstrate that Trim32 is a ubiquitin ligase that is expressed in skeletal muscle, can be induced upon muscle unloading and reloading, associates with myofibrils and is able to ubiquitinate actin, suggesting its likely participation in myofibrillar protein turnover, especially during muscle adaptation. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:413 / 424
页数:12
相关论文
共 51 条
[41]   THE REVERSIBLE DEPOLYMERIZATION OF ACTIN BY POTASSIUM IODIDE [J].
SZENTGYORGYI, AG .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1951, 31 (01) :97-103
[42]   The role of ubiquitin-proteasome-dependent proteolysis in the remodelling of skeletal muscle [J].
Taillandier, D ;
Combaret, L ;
Pouch, MN ;
Samuels, SE ;
Béchet, D ;
Attaix, D .
PROCEEDINGS OF THE NUTRITION SOCIETY, 2004, 63 (02) :357-361
[43]   Regulation of proteolysis during reloading of the unweighted soleus muscle [J].
Taillandier, D ;
Aurousseau, E ;
Combaret, L ;
Guezennec, CY ;
Attaix, D .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2003, 35 (05) :665-675
[44]   Expression of a calpastatin transgene slows muscle wasting and obviates changes in myosin isoform expression during murine muscle disuse [J].
Tidball, JG ;
Spencer, MJ .
JOURNAL OF PHYSIOLOGY-LONDON, 2002, 545 (03) :819-828
[45]  
TRINICK JA, 1982, METHOD ENZYMOL, V85, P17
[46]   MID1, mutated in Opitz syndrome, encodes an ubiquitin ligase that targets phosphatase 2A for degradation [J].
Trockenbacher, A ;
Suckow, V ;
Foerster, J ;
Winter, J ;
Krauss, S ;
Ropers, HH ;
Schneider, R ;
Schweiger, S .
NATURE GENETICS, 2001, 29 (03) :287-294
[47]   Efp targets 14-3-3σ for proteolysis and promotes breast tumour growth [J].
Urano, T ;
Saito, T ;
Tsukui, T ;
Fujita, M ;
Hosoi, T ;
Muramatsu, M ;
Ouchi, Y ;
Inoue, S .
NATURE, 2002, 417 (6891) :871-875
[48]   E3 ubiquitin liqase activity of the trifunctional ARD1 (ADP-riblosylation factor domain protein 1) [J].
Vichi, A ;
Payne, DM ;
Pacheco-Rodriguez, G ;
Moss, J ;
Vaughan, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (06) :1945-1950
[49]   Genew: The Human Gene Nomenclature Database [J].
Wain, HM ;
Lush, M ;
Ducluzeau, F ;
Povey, S .
NUCLEIC ACIDS RESEARCH, 2002, 30 (01) :169-171
[50]   MURF-1 and MURF-2 target a specific subset of myofibrillar proteins redundantly: Towards understanding MURF-dependent muscle ubiquitination [J].
Witt, SH ;
Granzier, H ;
Witt, CC ;
Labeit, S .
JOURNAL OF MOLECULAR BIOLOGY, 2005, 350 (04) :713-722