Association of Syncoilin and Desmin: LINKING INTERMEDIATE FILAMENT PROTEINS TO THE DYSTROPHIN-ASSOCIATED PROTEIN COMPLEX

Ellen Poon,Emily V Howman,Sarah E Newey,Kay E Davies

doi:10.1074/jbc.m105273200

Abstract

We recently identified a novel protein called syncoilin, a putative intermediate filament protein that interacts with alpha-dystrobrevin, a member of the dystrophin-associated protein complex. Syncoilin is found at the neuromuscular junction, sarcolemma, and Z-lines and is thought to be important for muscle fiber integrity. Based on the similar protein structure and cellular localization of syncoilin and desmin, we proposed that these proteins interact in vivo. The data presented confirm an interaction between syncoilin and desmin and demonstrate their co-localization in skeletal muscle. Intriguingly, whereas these proteins interact, COS-7 cell expression studies show that desmin and syncoilin do not assemble into heterofilaments. Furthermore, fractionation assay and immunofluorescence study of H2K myoblasts and myotubes suggest that, unlike typical intermediate filament proteins, syncoilin does not participate in filament formation with any protein. However, it is possible that syncoilin is involved in the anchoring of the desmin intermediate filament network at the sarcolemma and the neuromuscular junction. This interaction is likely to be important for maintaining muscle fiber integrity and may also link the dystrophin-associated protein complex to the cytoskeleton. The dysfunction or absence of syncoilin may result in the disruption of the intermediate filament network leading to muscle necrosis. Syncoilin is therefore an ideal candidate gene for muscular dystrophies and desmin-related myopathies.

Highlights

We recently identified a novel protein called syncoilin, a putative intermediate filament protein that interacts with ␣-dystrobrevin, a member of the dystrophin-associated protein complex
We describe an interaction between syncoilin and desmin, an association that may be important for linking the desmin intermediate filament network to the DAPC
We first identified syncoilin as a binding partner of ␣-dystrobrevin-1 and -2 using a yeast two-hybrid assay, and we classified the protein as a tentative member of the intermediate filament (IF) protein superfamily by sequence analysis [7]

Summary

Introduction

We recently identified a novel protein called syncoilin, a putative intermediate filament protein that interacts with ␣-dystrobrevin, a member of the dystrophin-associated protein complex. It is possible that syncoilin is involved in the anchoring of the desmin intermediate filament network at the sarcolemma and the neuromuscular junction. This interaction is likely to be important for maintaining muscle fiber integrity and may link the dystrophin-associated protein complex to the cytoskeleton. Syncoilin is a 64-kDa protein found in skeletal and cardiac muscle and was proposed to be a member of the intermediate filament (IF) protein superfamily based on sequence analysis [7]. In view of the structural roles generally performed by IF proteins, the association of syncoilin with ␣-dystrobrevin is important because it may provide an alternate route by which the DAPC links to components of the cytoskeleton, in this case, the IF network

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