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

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 (approximately 55 kDa and approximately 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.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

McElhinny AS,Perry CN,Witt CC,Labeit S,Gregorio CC

doi

10.1242/jcs.01158

keywords:

subject

Has Abstract

pub_date

2004-07-01 00:00:00

pages

3175-88

issue

Pt 15

eissn

0021-9533

issn

1477-9137

pii

jcs.01158

journal_volume

117

pub_type

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