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Cell Tissue Res (2015) 360:591608
DOI 10.1007/s00441-014-2016-4
REVIEW
Desmin in muscle and associated diseases: beyond the structural function
Karim Hnia & Caroline Ramspacher & Julien Vermot &
Jocelyn Laporte
Received: 19 August 2014 /Accepted: 22 September 2014 /Published online: 31 October 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Desmin is a muscle-specific type III intermediate filament essential for proper muscular structure and function. In human, mutations affecting desmin expression or promoting its aggregation lead to skeletal (desmin-related myopathies), or cardiac (desmin-related cardiomyopathy) pheno-types, or both. Patient muscles display intracellular accumulations of misfolded proteins and desmin-positive insoluble granulofilamentous aggregates, leading to a large spectrum of molecular alterations. Increasing evidence shows that desmin function is not limited to the structural and mechanical integrity of cells. This novel perception is strongly supported by the finding that diseases featuring desmin aggregates cannot be easily associated with mechanical defects, but rather involve desmin filaments in a broader spectrum of functions, such as in organelle positioning and integrity and in signaling. Here, we review desmin functions and related diseases affecting striated muscles. We detail emergent cellular functions of
desmin based on reported phenotypes in patients and animal models. We discuss known desmin protein partners and propose an overview of the way that this molecular network could serve as a signal transduction platform necessary for proper muscle function.
Keywords Intermediate filament . Desmin . Striated muscle . Cardiomyopathy . Myopathy
Intermediate filaments
Classification, structure and biochemical properties
The intermediate filament (IF) protein family encompasses 73 members encoded by a large group of genes that have been commonly implicated in human disease accounting for at least 94 different disease entities (Eriksson et al. 2009). IF family members have been subdivided into five distinct types on the basis of their primary structure, their properties of assembly and their developmentally regulated tissue-specific expression pattern (Fig. 1a). IF types I and II, which are composed of keratins, form obligatory heteropolymers in epithelial cells. By contrast, type III IF proteins, which include desmin, syncoilin, vimentin, peripherin and GFAP (glial fibrillary acidic protein), form homopolymers. The type IV group comprises three neurofilament (NF) subunits (NF-L [light], NF-M [middle] and NF-H [heavy]), -internexin, nestin and synemin and . Group V is composed of the nuclear IF proteins (lamin A,...