Muscle-specific RING finger-2 (MURF-2) is important for microtubule, intermediate filament and sarcomeric M-line maintenance in striated muscle development

Abigail S. McElhinny, Cynthia N. Perry, Christian C. Witt, Siegfried Labeit, Carol C. Gregorio

Research output: Contribution to journalReview article

73 Scopus citations

Abstract

The efficient functioning of striated muscle is dependent upon the structure of several cytoskeletal networks including myofibrils, microtubules, and intermediate filaments. However, little is known about how these networks function together during muscle differentiation and maintenance. In vitro studies suggest that members of the muscle-specific RING finger protein family (MURF-1, 2, and 3) act as cytoskeletal adaptors and signaling molecules by associating with myofibril components (including the giant protein, titin), microtubules and/or nuclear factors. We investigated the role of MURF-2, the least-characterized family member, in primary cultures of embryonic chick skeletal and cardiac myocytes. MURF-2 is detected as two species (∼55 kDa and ∼60 kDa) in embryonic muscle, which are down-regulated in adult muscle. Although predominantly located diffusely in the cytoplasm, MURF-2 also colocalizes with a sub-group of microtubules and the M-line region of titin. Reducing MURF-2 levels in cardiac myocytes using antisense oligonucleotides perturbed the structure of stable microtubule populations, the intermediate filament proteins desmin and vimentin, and the sarcomeric M-line region. In contrast, other sarcomeric regions and dynamic microtubules remained unaffected. MURF-2 knock-down studies in skeletal myoblasts also delayed myoblast fusion and myofibrillogenesis. Furthermore, contractile activity was also affected. We speculate that some of the roles of MURF-2 are modulated via titin-based mechanisms.

Original languageEnglish (US)
Pages (from-to)3175-3188
Number of pages14
JournalJournal of Cell Science
Volume117
Issue number15
DOIs
StatePublished - Jul 1 2004

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Keywords

  • M-line
  • MURF
  • Microtubules
  • Myofibrillogenesis
  • Myofibrils
  • Titin

ASJC Scopus subject areas

  • Cell Biology

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