title: Skeletal muscle intermediate filaments form a stress-transmitting and stress-signaling network.
abstract: A fundamental requirement of cells is their ability to transduce and interpret their mechanical environment. This ability contributes to regulation of growth, differentiation and adaptation in many cell types. The intermediate filament (IF) system not only provides passive structural support to the cell, but recent evidence points to IF involvement in active biological processes such as signaling, mechanotransduction and gene regulation. However, the mechanisms that underlie these processes are not well known. Skeletal muscle cells provide a convenient system to understand IF function because the major muscle-specific IF, desmin, is expressed in high abundance and is highly organized. Here, we show that desmin plays both structural and regulatory roles in muscle cells by demonstrating that desmin is required for the maintenance of myofibrillar alignment, nuclear deformation, stress production and JNK-mediated stress sensing. Finite element modeling of the muscle IF system suggests that desmin immediately below the sarcolemma is the most functionally significant. This demonstration of biomechanical integration by the desmin IF system suggests that it plays an active biological role in muscle in addition to its accepted structural role.
authors.affiliation: Departments of Orthopaedics, Bioengineering, Medicine and the Biomedical Sciences Graduate Group, University of California and Veterans Administration Medical Centers, San Diego, CA 92093, USA.
authors.forename: Michelle G
authors.initials: MG
authors.lastname: Palmisano
authors.affiliation: Departments of Orthopaedics, Bioengineering, Medicine and the Biomedical Sciences Graduate Group, University of California and Veterans Administration Medical Centers, San Diego, CA 92093, USA.
authors.forename: Shannon N
authors.initials: SN
authors.lastname: Bremner
authors.affiliation: Department of Comparative Biology, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: Troy A
authors.initials: TA
authors.lastname: Hornberger
authors.affiliation: Departments of Orthopaedics, Bioengineering, Medicine and the Biomedical Sciences Graduate Group, University of California and Veterans Administration Medical Centers, San Diego, CA 92093, USA.
authors.forename: Gretchen A
authors.initials: GA
authors.lastname: Meyer
authors.affiliation: Departments of Orthopaedics, Bioengineering, Medicine and the Biomedical Sciences Graduate Group, University of California and Veterans Administration Medical Centers, San Diego, CA 92093, USA.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Domenighetti
authors.affiliation: Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA.
authors.forename: Sameer B
authors.initials: SB
authors.lastname: Shah
authors.affiliation: MTA-SE Molecular Biophysics Research Group, Department and Radiation Biology, Semmelweis, University, Budapest 1094, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Kiss
authors.affiliation: MTA-SE Molecular Biophysics Research Group, Department and Radiation Biology, Semmelweis, University, Budapest 1094, Hungary.
authors.forename: Miklos
authors.initials: M
authors.lastname: Kellermayer
authors.affiliation: Department of Otolaryngology, University of California and Veterans Administration Medical Centers, San Diego, CA 92161, USA.
authors.forename: Allen F
authors.initials: AF
authors.lastname: Ryan
authors.affiliation: Departments of Orthopaedics, Bioengineering, Medicine and the Biomedical Sciences Graduate Group, University of California and Veterans Administration Medical Centers, San Diego, CA 92093, USA rlieber@ucsd.edu.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Lieber
mesh_terms: D000818:Animals; D003893:Desmin / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007382:Intermediate Filaments / Q000378:metabolism* / Q000648:ultrastructure; D040542:Mechanotransduction, Cellular / Q000235:genetics; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000648:ultrastructure; D009210:Myofibrils / Q000378:metabolism* / Q000648:ultrastructure; D012508:Sarcolemma / Q000235:genetics / Q000378:metabolism; D013314:Stress, Mechanical
chemical_list: D003893:Desmin
keywords: Biomechanics; Desmin; Mechanotransduction; Tensegrity