The muscle ankyrin repeat proteins: CARP, ankrd2/Arpp and DARP as a family of titin filament-based stress response molecules

J Mol Biol. 2003 Nov 7;333(5):951-64. doi: 10.1016/j.jmb.2003.09.012.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Base Sequence
  • Connectin
  • Conserved Sequence
  • Humans
  • Molecular Sequence Data
  • Muscle Proteins / physiology*
  • Muscle, Skeletal / physiology
  • Myocardium / metabolism
  • Nuclear Proteins / physiology*
  • Protein Kinases / physiology*
  • Repressor Proteins / physiology*


  • ANKRD1 protein, human
  • ANKRD2 protein, human
  • ANKRD23 protein, human
  • Ankrd1 protein, rat
  • Ankrd2 protein, mouse
  • Connectin
  • Muscle Proteins
  • Nuclear Proteins
  • Repressor Proteins
  • TTN protein, human
  • Protein Kinases