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Differential Expression of Titin and Obscurin mRNA in Striated Muscles of the Long-Tailed Ground Squirrel Urocitellus undulatus

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Abstract

Seasonal changes in mRNA levels of the giant sarcomeric cytoskeletal proteins titin and obscurin were studied in the skeletal m. longissimus dorsi and the cardiac (left ventricular) muscle in the long-tailed ground squirrel Urocitellus undulatus using real-time RT-PCR. The animals were divided into the following experimental groups: “summer activity”, “fall activity”, “hypothermia” (hibernation), “winter activity” (n = 5 per group). In the cardiac muscle of “hypothermia” animals, titin mRNA levels decreased by 28% (p ≤ 0.01); in the other three groups, no statistically significant differences in this parameter were found. In m. longissimus dorsi of “hypothermia” and “winter activity” animals, titin mRNA levels increased by 2.9 (p ≤ 0.01) and 3.6 (p ≤ 0.01) times, respectively, with no statistically significant differences in this parameter in “summer activity” and “fall activity” animals. Obscurin mRNA levels increased by 3.4–3.6 times (p ≤ 0.01) in the cardiac muscle of “fall activity”, “hypothermia” and “winter activity” animals, and by 3.0 and 3.6 times (p ≤ 0.01) in the skeletal muscle of “hypothermia” and “winter activity” animals, respectively. Thus, we report here for the first time the data on the differential expression of titin and obscurin mRNAs, indicating concerted changes in the giant cytoskeletal proteins in muscles of the long-tailed ground squirrel during hibernation. The results are discussed in the context of striated muscle adaptation to hibernation in this rodent species.

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Abbreviations

MyHC:

myosin heavy chains

mRNA:

matrix ribonucleic acid

RT-PCR:

reverse transcription polymerase chain reaction

REFERENCES

  1. Brauch KM, Dhruv ND, Hanse EA, Andrews MT (2005) Digital transcriptome analysis indicates adaptive mechanisms in the heart of a hibernating mammal. Physiol Genomics 23(2): 227–234. https://doi.org/10.1152/physiolgenomics.00076.2005

    Article  CAS  PubMed  Google Scholar 

  2. Williams DR, Epperson LE, Li W, Hughes MA, Taylor R, Rogers J, Martin SL, Cossins AR, Gracey AY (2005) Seasonally hibernating phenotype assessed through transcript screening. Physiol Genomics 24(1): 13–22. https://doi.org/10.1152/physiolgenomics.00301.2004

    Article  PubMed  Google Scholar 

  3. Yan J, Barnes BM, Kohl F, Marr TG (2008) Modulation of gene expression in hibernating arctic ground squirrels. Physiol Genomics 32(2): 170–181. https://doi.org/10.1152/physiolgenomics.00075.2007

    Article  CAS  PubMed  Google Scholar 

  4. Hampton M, Melvin RG, Kendall AH, Kirkpatrick BR, Peterson N, Andrews MT (2011) Deep sequencing the transcriptome reveals seasonal adaptive mechanisms in a hibernating mammal. PLoS One 6(10): e27021. https://doi.org/10.1371/journal.pone.0027021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Vermillion KL, Anderson KJ, Hampton M, Andrews MT (2015) Gene expression changes controlling distinct adaptations in the heart and skeletal muscle of a hibernating mammal. Physiol Genomics 47(3): 58–74. https://doi.org/10.1152/physiolgenomics.00108.2014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bogren LK, Grabek KR, Barsh GS, Martin SL (2017) Comparative tissue transcriptomics highlights dynamic differences among tissues but conserved metabolic transcript prioritization in preparation for arousal from torpor. J Comp Physiol B 187: 735–748. https://doi.org/10.1007/s00360-017-1073-x

    Article  CAS  PubMed  Google Scholar 

  7. Chang H, Jiang S, Ma X, Peng X, Zhang J, Wang Z, Xu S, Wang H, Gao Y (2018) Proteomic analysis reveals the distinct energy and protein metabolism characteristics involved in myofiber type conversion and resistance of atrophy in the extensor digitorum longus muscle of hibernating Daurian ground squirrels. Comp Biochem Physiol Part D: Genomics Proteomics 26: 20–31. https://doi.org/10.1016/j.cbd.2018.02.002

    Article  CAS  Google Scholar 

  8. Andrews MT (2019) Molecular interactions underpinning the phenotype of hibernation in mammals. J Exp Biol 222(2): jeb160606. https://doi.org/10.1242/jeb.160606

    Article  PubMed  Google Scholar 

  9. Vikhlyantsev IM, Karaduleva EV, Podlubnaya ZA (2008) Seasonal changes in the composition of titin isoforms in muscles of hibernating ground squirrels. Biophysics 53: 598–603. https://doi.org/10.1134/S0006350908060249

    Article  Google Scholar 

  10. Salmov NN, Vikhlyantsev IM, Ulanova AD, Gritsyna YV, Bobylev AG, Saveljev AP, Makariushchenko VV, Maksudov GY, Podlubnaya ZA (2015) Seasonal changes in isoform composition of giant proteins of thick and thin filaments and titin (connectin) phosphorylation level in striated muscles of bears (Ursidae, Mammalia). Biochemistry (Mosc) 80(3): 343–355. https://doi.org/10.1134/S0006297915030098

  11. Salmov NN, Gritsyna YV, Ulanova AD, Vikhlyantsev IM, Podlubnaya ZA (2015) On the role of titin phosphorylation in the development of muscular atrophy. Biophysics 60: 684–686. https://doi.org/10.1134/S0006350915040193

    Article  CAS  Google Scholar 

  12. Popova S, Ulanova A, Gritsyna Y, Salmov N, Rogachevsky V, Mikhailova G, Bobylev A, Bobyleva L, Yutskevich Y, Morenkov O, Zakharova N, Vikhlyantsev I (2020) Predominant synthesis of giant myofibrillar proteins in striated muscles of the long-tailed ground squirrel Urocitellus undulatus during interbout arousal. Sci Rep 10(1): 15185. https://doi.org/10.1038/s41598-020-72127-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Popova SS, Yurshenas DA, Mikhailova GZ, Bobyleva LG, Salmov NN, Tyapkina OV, Nurullin LF, Gazizova GR, Nigmetzyanov IR, Gusev OA, Zakharova NM, Vikhlyantsev IM (2021) Stable Level of Giant Sarcomeric Cytoskeletal Proteins in Striated Muscles of the Edible Dormouse Glis glis during Hibernation. J Evol Biochem Phys 57: 886–895. https://doi.org/10.1134/S0022093021040128

    Article  CAS  Google Scholar 

  14. Vikhlyantsev IM, Podlubnaya ZA (2012) New titin (connectin) isoforms and their functional role in striated muscles of mammals: facts and suppositions. Biochemistry (Mosc) 77(13): 1515–1535. https://doi.org/10.1134/S0006297912130093

  15. Loescher CM, Hobbach AJ, Linke WA (2021) Titin (TTN): from molecule to modifications, mechanics and medical significance. Cardiovasc Res 2021: cvab328 https://doi.org/10.1093/cvr/cvab328.

    Article  Google Scholar 

  16. Knight JE, Narus EN, Martin SL, Jacobson A, Barnes BM, Boyer BB (2000) mRNA stability and polysome loss in hibernating Arctic ground squirrels (Spermophilus parryii). Mol Cell Biol 20(17): 6374–6379. https://doi.org/10.1128/MCB.20.17.6374-6379.2000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Grabek KR, Diniz Behn C, Barsh GS, Hesselberth JR, Martin SL (2015) Enhanced stability and polyadenylation of select mRNAs support rapid thermogenesis in the brown fat of a hibernator. eLife 4: e04517. https://doi.org/10.7554/eLife.04517

    Article  PubMed Central  Google Scholar 

  18. van Breukelen F, Martin SL (2002) Reversible depression of transcription during hibernation. J Comp Physiol B 172(5): 355–361. https://doi.org/10.1007/s00360-002-0256-1

    Article  CAS  PubMed  Google Scholar 

  19. Kontrogianni-Konstantopoulos A, Ackermann MA, Bowman AL, Yap SV, Bloch RJ (2009) Muscle giants: molecular scaffolds in sarcomerogenesis. Physiol Rev 89(4): 1217–1267. https://doi.org/10.1152/physrev.00017.2009

    Article  CAS  PubMed  Google Scholar 

  20. Manring HR, Carter OA, Ackermann MA (2017) Obscure functions: the location-function relationship of obscurins. Biophys Rev 9(3): 245–258. https://doi.org/10.1007/s12551-017-0254-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Zakharova NM (2014) Some features of body warming at provoked awakening of hibernating ground squirrels Spermophilus undulatus. Fundament issled 6: 1401–1405. https://fundamental-research.ru/ru/article/view?id=34350

    Google Scholar 

  22. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method Methods 25(4): 402–408. https://doi.org/10.1006/meth.2001.1262

  23. Cotton CJ (2016) Skeletal muscle mass and composition during mammalian hibernation. J Exp Biol 219(2): 226–234. https://doi.org/10.1242/jeb.125401

    Article  PubMed  Google Scholar 

  24. Lazareva MV, Trapeznikova KO, Vikhliantsev IM, Bobylev AG, Klimov AA, Podlubnaia ZA (2012) Seasonal changes in the isoform composition of the myosin heavy chains in skeletal muscles of hibernating ground squirrels Spermophilus undulatus. Biophysics 57: 764–768. https://doi.org/10.1134/S0006350912060085

    Article  CAS  Google Scholar 

  25. Morin P Jr, Storey KB (2009) Mammalian hibernation: differential gene expression and novel application of epigenetic controls. Int J Dev Biol 53(2-3): 433–442. https://pubmed.ncbi.nlm.nih.gov/19412897/

    Article  CAS  PubMed  Google Scholar 

  26. Benian GM, Mayans O (2015) Titin and obscurin: giants holding hands and discovery of a new Ig domain subset. J Mol Biol 427(4): 707–714. https://doi.org/10.1016/j.jmb.2014.12.017

    Article  CAS  PubMed  Google Scholar 

  27. Ackermann MA, Shriver M, Perry NA, Hu LY, Kontrogianni-Konstantopoulos A (2014) Obscurins: Goliaths and Davids take over non-muscle tissues. PLoS One 9(2): e88162. https://doi.org/10.1371/journal.pone.0190842

    Article  PubMed  PubMed Central  Google Scholar 

  28. Young P, Ehler E, Gautel M (2001) Obscurin, a giant sarcomeric Rho guanine nucleotide exchange factor protein involved in sarcomere assembly. J Cell Biol 154(1): 123–136. https://doi.org/10.1083/jcb.200102110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Bang ML, Centner T, Fornoff F, Geach AJ, Gotthardt M, McNabb M, Witt CC, Labeit D, Gregorio CC, Granzier H, Labeit S (2001) The complete gene sequence of titin, expression of an unusual approximately 700-kDa titin isoform, and its interaction with obscurin identify a novel Z-line to I-band linking system. Circ Res 89(11): 1065–10672. https://doi.org/10.1161/hh2301.100981

    Article  CAS  PubMed  Google Scholar 

  30. Bowman AL, Catino DH, Strong JC, Randall WR, Kontrogianni-Konstantopoulos A, Bloch RJ (2008) The rho-guanine nucleotide exchange factor domain of obscurin regulates assembly of titin at the Z-disk through interactions with Ran binding protein 9. Mol Biol Cell 19(9): 3782–3792. https://doi.org/10.1091/mbc.e08-03-0237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Bagnato P, Barone V, Giacomello E, Rossi D, Sorrentino V (2003) Binding of an ankyrin-1 isoform to obscurin suggests a molecular link between the sarcoplasmic reticulum and myofibrils in striated muscles. J Cell Biol 160(2): 245–253. https://doi.org/10.1083/jcb.200208109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kontrogianni-Konstantopoulos A, Jones EM, Van Rossum DB, Bloch RJ (2003) Obscurin is a ligand for small ankyrin 1 in skeletal muscle. Mol Biol Cell 14(3): 1138–1148. https://doi.org/10.1091/mbc.e02-07-0411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Randazzo D, Giacomello E, Lorenzini S, Rossi D, Pierantozzi E, Blaauw B, Reggiani C, Lange S, Peter AK, Chen J, Sorrentino V (2013) Obscurin is required for ankyrinB-dependent dystrophin localization and sarcolemma integrity. J Cell Biol 200(4): 523–536. https://doi.org/10.1083/jcb.201205118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Chopard A, Arrighi N, Carnino A, Marini JF (2005) Changes in dysferlin, proteins from dystrophin glycoprotein complex, costameres, and cytoskeleton in human soleus and vastus lateralis muscles after a long-term bedrest with or without exercise. FASEB J 19(12): 1722–1724. https://doi.org/10.1096/fj.04-3336fje

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by the Russian Foundation for Basic Research (RFBR), grant no. 20-04-00204.

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Authors and Affiliations

  1. Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region, Russia

    Yu. V. Gritsyna, M. A. Grabarskaya, G. Z. Mikhailova, S. S. Popova, L. G. Bobyleva, A. M. Ermakov & I. M. Vikhlyantsev

  2. Institute of Cell Biophysics, FRC PSCBR, Russian Academy of Sciences, Pushchino, Moscow Region, Russia

    N. M. Zakharova

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  1. Yu. V. Gritsyna
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  8. I. M. Vikhlyantsev
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Contributions

Conceptualization and experimental design (Yu.V.G., I.M.V.); data collection (Yu.V.G., S.S.P., A.M.E.); data processing (Yu.V.G., G.Z.M., M.A.G., I.M.V.); writing and editing the manuscript (Yu.V.G., G.Z.M., L.G.B., N.M.Z., I.M.V.).

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Correspondence to I. M. Vikhlyantsev.

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The authors declare that they have neither evident nor potential conflict of interest associated with the publication of this article.

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Translated by A. Polyanovsky

Russian Text © The Author(s), 2022, published in Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, 2022, Vol. 58, No. 5, pp. 404–411https://doi.org/10.31857/S0044452922050047.

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Gritsyna, Y.V., Grabarskaya, M.A., Mikhailova, G.Z. et al. Differential Expression of Titin and Obscurin mRNA in Striated Muscles of the Long-Tailed Ground Squirrel Urocitellus undulatus. J Evol Biochem Phys 58, 1332–1340 (2022). https://doi.org/10.1134/S0022093022050052

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