The muscle ankyrin repeat proteins: CARP, ankrd2/Arpp and DARP as a family of titin filament-based stress response molecules.
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.
Department of Cell Biology and Anatomy, University of Arizona, Tucson, AZ 85724, USA.
Melanie K
MK
Miller
Marie-Louise
ML
Bang
Christian C
CC
Witt
Dietmar
D
Labeit
Charles
C
Trombitas
Kaori
K
Watanabe
Henk
H
Granzier
Abigail S
AS
McElhinny
Carol C
CC
Gregorio
Siegfried
S
Labeit
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001483:Base Sequence; D064211:Connectin; D017124:Conserved Sequence; D006801:Humans; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D009687:Nuclear Proteins / Q000502:physiology*; D011494:Protein Kinases / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology*
C491304:ANKRD1 protein, human; C432364:ANKRD2 protein, human; C472289:ANKRD23 protein, human; C491303:Ankrd1 protein, rat; C485877:Ankrd2 protein, mouse; D064211:Connectin; D009124:Muscle Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C577285:TTN protein, human; D011494:Protein Kinases