title: Synemin acts as a regulator of signalling molecules during skeletal muscle hypertrophy.
abstract: Synemin, a type IV intermediate filament (IF) protein, forms a bridge between IFs and cellular membranes. As an A-kinase-anchoring protein, it also provides temporal and spatial targeting of protein kinase A (PKA). However, little is known about its functional roles in either process. To better understand its functions in muscle tissue, we generated synemin-deficient (Synm(-) (/-)) mice. Synm(-) (/-) mice displayed normal development and fertility but showed a mild degeneration and regeneration phenotype in myofibres and defects in sarcolemma membranes. Following mechanical overload, Synm(-) (/-) mice muscles showed a higher hypertrophic capacity with increased maximal force and fatigue resistance compared with control mice. At the molecular level, increased remodelling capacity was accompanied by decreased myostatin (also known as GDF8) and atrogin (also known as FBXO32) expression, and increased follistatin expression. Furthermore, the activity of muscle-mass control molecules (the PKA RIIα subunit, p70S6K and CREB1) was increased in mutant mice. Finally, analysis of muscle satellite cell behaviour suggested that the absence of synemin could affect the balance between self-renewal and differentiation of these cells. Taken together, our results show that synemin is necessary to maintain membrane integrity and regulates signalling molecules during muscle hypertrophy.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR CNRS 8256/INSERM ERL U1164, Biological Adaptation and Ageing, Institut de Biologie Paris-Seine, Paris, F-75005 France zhenlin.li@upmc.fr onnik.agbulut@upmc.fr.
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Li
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR CNRS 8256/INSERM ERL U1164, Biological Adaptation and Ageing, Institut de Biologie Paris-Seine, Paris, F-75005 France.
authors.forename: Ara
authors.initials: A
authors.lastname: Parlakian
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR CNRS 8256/INSERM ERL U1164, Biological Adaptation and Ageing, Institut de Biologie Paris-Seine, Paris, F-75005 France.
authors.forename: Dario
authors.initials: D
authors.lastname: Coletti
authors.affiliation: Sorbonne Universités, UPMC Univ-Paris 06, INSERM U974, CNRS UMR7215, Institut de Myologie, Paris-France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Alonso-Martin
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR CNRS 8256/INSERM ERL U1164, Biological Adaptation and Ageing, Institut de Biologie Paris-Seine, Paris, F-75005 France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Hourdé
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR CNRS 8256/INSERM ERL U1164, Biological Adaptation and Ageing, Institut de Biologie Paris-Seine, Paris, F-75005 France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Joanne
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR CNRS 8256/INSERM ERL U1164, Biological Adaptation and Ageing, Institut de Biologie Paris-Seine, Paris, F-75005 France.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Gao-Li
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR CNRS 8256/INSERM ERL U1164, Biological Adaptation and Ageing, Institut de Biologie Paris-Seine, Paris, F-75005 France.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Blanc
authors.affiliation: Sorbonne Universités, UPMC Univ-Paris 06, INSERM U974, CNRS UMR7215, Institut de Myologie, Paris-France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Ferry
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR CNRS 8256/INSERM ERL U1164, Biological Adaptation and Ageing, Institut de Biologie Paris-Seine, Paris, F-75005 France.
authors.forename: Denise
authors.initials: D
authors.lastname: Paulin
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR CNRS 8256/INSERM ERL U1164, Biological Adaptation and Ageing, Institut de Biologie Paris-Seine, Paris, F-75005 France.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Xue
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR CNRS 8256/INSERM ERL U1164, Biological Adaptation and Ageing, Institut de Biologie Paris-Seine, Paris, F-75005 France zhenlin.li@upmc.fr onnik.agbulut@upmc.fr.
authors.forename: Onnik
authors.initials: O
authors.lastname: Agbulut
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D003893:Desmin / Q000235:genetics / Q000378:metabolism; D006984:Hypertrophy / Q000378:metabolism* / Q000473:pathology; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D009135:Muscular Diseases / Q000235:genetics / Q000378:metabolism*
chemical_list: D003893:Desmin; D007381:Intermediate Filament Proteins; C491443:synemin protein, mouse
keywords: Desmin; Intermediate filament; Muscle hypertrophy; Skeletal muscle