Role of troponin T in disease

被引:58
作者
Gomes, AV
Barnes, JA
Harada, K
Potter, JD
机构
[1] Univ Miami, Sch Med, Dept Mol & Cellular Pharmacol, Miami, FL 33136 USA
[2] Univ W Indies, Biochem Unit, St Augustine, Trinidad Tobago
关键词
troponin T; calcium; muscle contraction; nemaline myopathy; dilated cardiomyopathy; hypertrophic cardiomyopathy;
D O I
10.1023/B:MCBI.0000041853.20588.a0
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Several striated muscle myopathies have been directly linked to mutations in contractile and associated proteins. Troponin T (TnT) is one of the three subunits that form troponin (Tn) which together with tropomyosin is responsible for the regulation of striated muscle contraction. All three subunits of cardiac Tn as well as tropomyosin have been associated with hypertrophic cardiomyopathy (HCM). However, TnT accounts for most of the mutations that cause HCM in these regulatory proteins. To date 30 mutations have been identified in the cardiac TnT (CTnT) gene that results in familial HCM (FHC). The CTnT gene has also been associated with familial dilated cardiomyopathy (DCM). CTnT deficiency is lethal due to impaired cardiac development. A recessive nonsense mutation in the gene encoding slow skeletal TnT has been associated with an unusual, severe form of nemaline myopathy among the Old Order Amish. How each mutation leads to the diverse clinical symptoms associated with FHC, DCM or nemaline myopathy is unclear. However, the use of animal model systems, in particular transgenic mice, has significantly increased our knowledge of normal and myopathic muscle physiology. In this review, we focus on the role of TnT in muscle physiology and disease.
引用
收藏
页码:115 / 129
页数:15
相关论文
共 101 条
[1]   Prevalence and age-dependence of malignant mutations in the beta-myosin heavy chain and troponin T genes in hypertrophic cardiomyopathy - A comprehensive outpatient perspective [J].
Ackerman, MJ ;
VanDriest, SL ;
Ommen, SR ;
Will, ML ;
Nishimura, RA ;
Tajik, AJ ;
Gersh, BJ .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2002, 39 (12) :2042-2048
[2]   Patients with familial hypertrophic cardiomyopathy caused by a Phe110Ile missense mutation in the cardiac troponin T gene have variable cardiac morphologies and a favorable prognosis [J].
Anan, R ;
Shono, H ;
Kisanuki, A ;
Arima, S ;
Nakao, S ;
Tanaka, H .
CIRCULATION, 1998, 98 (05) :391-397
[3]   Precocious expression of cardiac troponin T in early chick embryos is independent of bone morphogenetic protein signaling (vol 225, pg 376, 2002) [J].
Antin, PB ;
Zhang, WJ ;
Bales, MA ;
Garriock, RJ ;
Yatskievych, TA .
DEVELOPMENTAL DYNAMICS, 2002, 225 (03) :376-376
[4]  
BIESIADECKI BJ, 2002, J BIOL CHEM, V107
[5]   CARDIAC MYOSIN BINDING PROTEIN-C GENE SPLICE ACCEPTOR SITE MUTATION IS ASSOCIATED WITH FAMILIAL HYPERTROPHIC CARDIOMYOPATHY [J].
BONNE, G ;
CARRIER, L ;
BERCOVICI, J ;
CRUAUD, C ;
RICHARD, P ;
HAINQUE, B ;
GAUTEL, M ;
LABEIT, S ;
JAMES, M ;
BECKMANN, J ;
WEISSENBACH, J ;
VOSBERG, HP ;
FISZMAN, M ;
KOMAJDA, M ;
SCHWARTZ, K .
NATURE GENETICS, 1995, 11 (04) :438-440
[6]  
D'Cruz L G, 2000, J Med Genet, V37, pE18, DOI 10.1136/jmg.37.9.e18
[7]   Mutations in the β-tropomyosin (TPM2) gene -: a rare cause of nemaline myopathy [J].
Donner, K ;
Ollikainen, M ;
Ridanpää, M ;
Christen, HJ ;
Goebel, HH ;
de Visser, M ;
Pelin, K ;
Wallgren-Pettersson, C .
NEUROMUSCULAR DISORDERS, 2002, 12 (02) :151-158
[8]   De novo missense mutation in a constitutively expressed exon of the slow alpha-tropomyosin gene TPM3 associated with an atypical, sporadic case of nemaline myopathy [J].
Durling, HJ ;
Reilich, P ;
Müller-Höcker, J ;
Mendel, B ;
Pongratz, D ;
Wallgren-Petersson, C ;
Gunning, P ;
Lochmüller, H ;
Laing, NG .
NEUROMUSCULAR DISORDERS, 2002, 12 (10) :947-951
[9]  
EBASHI S, 1976, J BIOCHEM-TOKYO, V79, pP48
[10]   Late-onset hypertrophic cardiomyopathy caused by a mutation in the cardiac troponin T gene [J].
Elliott, PM ;
D'Cruz, L ;
McKenna, WJ .
NEW ENGLAND JOURNAL OF MEDICINE, 1999, 341 (24) :1855-1856