TY - JOUR
T1 - The muscle ankyrin repeat proteins
T2 - CARP, ankrd2/Arpp and DARP as a family of titin filament-based stress response molecules
AU - Miller, Melanie K.
AU - Bang, Marie Louise
AU - Witt, Christian C.
AU - Labeit, Dietmar
AU - Trombitas, Charles
AU - Watanabe, Kaori
AU - Granzier, Henk
AU - McElhinny, Abigail S.
AU - Gregorio, Carol C.
AU - Labeit, Siegfried
N1 - Funding Information:
The authors thank Ryan Mudry for help with microscopy and Figures, Stacy Stanislaw for technical assistance, and Joe Bahl and Yewen Wu for cell isolation. We are indebted to Professor H. Sorimachi for his advice and provision of p94 constructs. This work was supported by the Deutsche Forschungsgemeinschaft (La668/7-1) (to S.L.), the NIH HL062881 (to H.G.) and HL63926 and HL03985 (to C.C.G.), and the American Heart Association 0120586Z (to A.S.M.).
PY - 2003/11/7
Y1 - 2003/11/7
N2 - CARP, ankrd-2/Arpp, and DARP, are three members of a conserved gene family, referred to here as MARPs (muscle ankyrin repeat proteins). The expression of MARPs is induced upon injury and hypertrophy (CARP), stretch or denervation (ankrd2/Arpp), and during recovery following starvation (DARP), suggesting that they are involved in muscle stress response pathways. Here, we show that MARP family members contain within their ankyrin repeat region a binding site for the myofibrillar elastic protein titin. Within the myofibril, MARPs, myopalladin, and the calpain protease p94 appear to be components of a titin N2A-based signaling complex. Ultrastructural studies demonstrated that all three endogenous MARP proteins co-localize with I-band titin N2A epitopes in adult heart muscle tissues. In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of CARP and DARP: staining for both proteins was increased in the nucleus and at the I-band region of myofibrils, while DARP staining also increased at intercalated discs. We speculate that the myofibrillar MARPs are regulated by stretch, and that this links titin-N2A-based myofibrillar stress/strain signals to a MARP-based regulation of muscle gene expression.
AB - CARP, ankrd-2/Arpp, and DARP, are three members of a conserved gene family, referred to here as MARPs (muscle ankyrin repeat proteins). The expression of MARPs is induced upon injury and hypertrophy (CARP), stretch or denervation (ankrd2/Arpp), and during recovery following starvation (DARP), suggesting that they are involved in muscle stress response pathways. Here, we show that MARP family members contain within their ankyrin repeat region a binding site for the myofibrillar elastic protein titin. Within the myofibril, MARPs, myopalladin, and the calpain protease p94 appear to be components of a titin N2A-based signaling complex. Ultrastructural studies demonstrated that all three endogenous MARP proteins co-localize with I-band titin N2A epitopes in adult heart muscle tissues. In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of CARP and DARP: staining for both proteins was increased in the nucleus and at the I-band region of myofibrils, while DARP staining also increased at intercalated discs. We speculate that the myofibrillar MARPs are regulated by stretch, and that this links titin-N2A-based myofibrillar stress/strain signals to a MARP-based regulation of muscle gene expression.
KW - Muscle ankyrin repeat proteins: CARP, ankrd2/Arpp and DARP
KW - Myofibrillar elasticity
KW - Stretch-dependent muscle gene expression
KW - Titin
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U2 - 10.1016/j.jmb.2003.09.012
DO - 10.1016/j.jmb.2003.09.012
M3 - Article
C2 - 14583192
AN - SCOPUS:0142247618
SN - 0022-2836
VL - 333
SP - 951
EP - 964
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 5
ER -