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

Melanie K. Miller, Marie Louise Bang, Christian C. Witt, Dietmar Labeit, Charles Trombitas, Kaori Watanabe, Henk Granzier, Abigail S. McElhinny, Carol C. Gregorio, Siegfried Labeit

Research output: Contribution to journalArticlepeer-review

245 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)951-964
Number of pages14
JournalJournal of Molecular Biology
Volume333
Issue number5
DOIs
StatePublished - Nov 7 2003

Keywords

  • Muscle ankyrin repeat proteins: CARP, ankrd2/Arpp and DARP
  • Myofibrillar elasticity
  • Stretch-dependent muscle gene expression
  • Titin

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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