Self-Assembly Incompetence of Synemin Is Related to the Property of Its Head and Rod Domains

Khanamiryan, Luiza; Li, Zhenlin; Paulin, Denise; Xue, Zhigang

doi:10.1021/bi800912w

Cited by 15 publications

(14 citation statements)

References 51 publications

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“…Synemin is present in two alternatively spliced forms, ␣ and ␤. Previous studies revealed synemin at different subcellular locations in cardiac and skeletal muscle, neurons, and glial cells (18,21,25,28,31) and showed that synemin interacts with several other proteins, including desmin, vimentin, ␣-actinin, and vinculin (14,20,21,25), which all bind to the ␤ isoform, with additional binding sites for vinculin and talin on ␣-synemin (26,27). Here we test the hypothesis that both isoforms of synemin are expressed in the developing heart and that each isoform associates with and differentially stabilizes distinct structures in cardiomyocytes.…”

Section: Resultsmentioning

confidence: 99%

“…Highly expressed in adult skeletal and cardiac muscle (13,14), synemin is also found in smooth muscle, neurons, glial cells, and hepatic stellate cells (15,18,19). In myocytes, synemin integrates into filaments containing desmin or vimentin via its rod domain (14,20,21). The rod domain of synemin can also interact with keratins 5 and 6 (22) (although these have not been identified in striated muscles) and 3 components of the dystroglycan complex: dystrophin, utrophin (23), and ␣-dystrobrevin (24).…”

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confidence: 99%

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Synemin isoforms differentially organize cell junctions and desmin filaments in neonatal cardiomyocytes

et al. 2011

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Intermediate filaments (IFs) in cardiomyocytes consist primarily of desmin, surround myofibrils at Z disks, and transmit forces from the contracting myofilaments to the cell surface through costameres at the sarcolemma and desmosomes at intercalated disks. Synemin is a type IV IF protein that forms filaments with desmin and also binds α-actinin and vinculin. Here we examine the roles and expression of the α and β forms of synemin in developing rat cardiomyocytes. Quantitative PCR showed low levels of expression for both synemin mRNAs, which peaked at postnatal day 7. Synemin was concentrated at sites of cell-cell adhesion and at Z disks in neonatal cardiomyocytes. Overexpression of the individual isoforms showed that α-synemin preferentially localized to cell-cell junctions, whereas β-synemin was primarily at the level of Z disks. An siRNA targeted to both synemin isoforms reduced protein expression in cardiomyocytes by 70% and resulted in a failure of desmin to align with Z disks and disrupted cell-cell junctions, with no effect on sarcomeric organization. Solubility assays showed that β-synemin was soluble and interacted with sarcomeric α-actinin by coimmunoprecipitation, while α-synemin and desmin were insoluble. We conclude that β-synemin mediates the association of desmin IFs with Z disks, whereas α-synemin stabilizes junctional complexes between cardiomyocytes.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Synemin isoforms differentially organize cell junctions and desmin filaments in neonatal cardiomyocytes

et al. 2011

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“…Synemin is unique in that it cannot homopolymerise to form filament networks, and therefore requires an appropriate copolymerisation partner, such as desmin, vimentin or keratin, depending on the cell type, to form filamentous structures (Bellin et al, 1999;Chourbagi et al, 2011;Hirako et al, 2003;Khanamiryan et al, 2008). Consequently, synemin filaments are unstable and delocalised in the cells of mice lacking desmin or vimentin (Carlsson et al, 2000;Izmiryan et al, 2006;Izmiryan et al, 2009;Jing et al, 2007;Xue et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Synemin acts as a regulator of signalling molecules in skeletal muscle hypertrophy

Li¹,

Parlakian²,

Coletti³

et al. 2014

Journal of Cell Science

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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 2/2 ) mice. Synm 2/2 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 2/2 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 RIIa 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.

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“…The two larger isoforms of synemin (H and M) harbor extended C-terminal tails that project from the surface of the filament and provide connecting arms that associate with neighboring proteins [5-7]. In contrast, the small isoform (L) lacks this tail domain [3,8]. …”

Section: Introductionmentioning

confidence: 99%

Dynamic expression of synemin isoforms in mouse embryonic stem cells and neural derivatives

et al. 2011

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BackgroundIntermediate filaments (IFs) are major components of the mammalian cytoskeleton and expressed in cell-type-specific patterns. Morphological changes during cell differentiation are linked to IF network remodeling. However, little is known concerning the presence and the role of IFs in embryonic stem (ES) cells and during their differentiation.ResultsWe have examined the expression profile of synemin isoforms in mouse pluripotent ES cells and during their neural differentiation induced by retinoic acid. Using RT-PCR, Western blotting and immunostaining, we show that synemin M is present at both mRNA and protein levels in undifferentiated ES cells as early as pluripotency factor Oct-3/4 and IF keratin 8. Synemin H was produced only in neural precursors when neural differentiation started, concurrently with synemin M, nestin and glial fibrillary acidic protein. However, both synemin H and M were restricted to the progenitor line during the neural differentiation program. Our in vivo analysis also confirmed the expression of synemins H/M in multipotent neural stem cells in the subventricular zone of the adult brain, a neurogenic germinal niche of the mice. Knocking down synemin in ES cells by shRNA lentiviral particles transduction has no influence on expression of Oct4, Nanog and SOX2, but decreased keratin 8 expression.ConclusionsOur study shows a developmental stage specific regulation of synemin isoforms in ES cells and its neural derivatives. These findings represent the first evidence that synemins could potentially be useful markers for distinguishing multipotent ES cells from undifferentiated neural stem cells and more committed progenitor cells.

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Self-Assembly Incompetence of Synemin Is Related to the Property of Its Head and Rod Domains

Cited by 15 publications

References 51 publications

Synemin isoforms differentially organize cell junctions and desmin filaments in neonatal cardiomyocytes

Synemin isoforms differentially organize cell junctions and desmin filaments in neonatal cardiomyocytes

Synemin acts as a regulator of signalling molecules in skeletal muscle hypertrophy

Dynamic expression of synemin isoforms in mouse embryonic stem cells and neural derivatives

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