Regulation of Microtubule Dynamics and Myogenic Differentiation by Murf, a Striated Muscle Ring-Finger Protein

Abstract

The RING-finger domain is a novel zinc-binding Cys-His protein motif found in a growing number of proteins involved in signal transduction, ubiquitination, gene transcription, differentiation, and morphogenesis. We describe a novel muscle-specific RING-finger protein (MURF) expressed specifically in cardiac and skeletal muscle cells throughout pre- and postnatal mouse development. MURF belongs to the RING-B-box-coiled-coil subclass of RING-finger proteins, characterized by an NH2-terminal RING-finger followed by a zinc-finger domain (B-box) and a leucine-rich coiled-coil domain. Expression of MURF is required for skeletal myoblast differentiation and myotube fusion. The leucine-rich coiled-coil domain of MURF mediates association with microtubules, whereas the RING-finger domain is required for microtubule stabilization and an additional region is required for homo-oligomerization. Expression of MURF establishes a cellular microtubule network that is resistant to microtubule depolymerization induced by alkaloids, cold and calcium. These results identify MURF as a myogenic regulator of the microtubule network of striated muscle cells and reveal a link between microtubule organization and myogenesis.

Loss of muscle-specific RING-finger 3 predisposes the heart to cardiac rupture after myocardial infarction

“…MuRF1, -2, and -3 all localize to the M-line and Z-disk (7,14,15) and form heterodimers (14), raising the possibility that the phenotype of MuRF3 mutant mice may reveal only a subset of MuRF3 functions due to redundancy among MuRF proteins. Further analysis of the functions of MuRF proteins in vivo and of the consequences of compound MuRF gene deletion should reveal additional functions for this family of proteins in cardiac, as well as skeletal, muscle.…”

“…Muscle-specific RING-finger (MuRF) proteins MuRF1, -2, and -3 comprise a subfamily of the RING-finger E3 ubiquitin ligases that are expressed specifically in cardiac and skeletal muscle (7). MuRF3, the first member of this family to be identified, associates with microtubules and is required for skeletal myoblast differentiation and development of cellular microtubular networks (7).…”

Generation of noncentrosomal microtubule arrays

“…The muscle-specific RING finger proteins MURF-2 and MURF-3 both regulate muscle differentiation by modulating MT stability and so probably play a part (McElhinny et al, 2004;Spencer et al, 2000).…”

Effects of fasting and refeeding on expression of MAFbx and MuRF1 in chick skeletal muscle

“…MAFbx, also known as atrogin1 and Fbxo32, contains an F-box domain that is characteristic of SCF-type E3 ubiquitin ligases [1,2]. MuRF1 is a muscle-specific RING-finger protein that binds the Cys-His zinc-binding motif [3]. MAFbx and MuRF1 are specifically expressed in cardiac and skeletal muscles and have vital roles in protein degradation during muscle wasting [4].…”