Cellular and Molecular Life Sciences

, Volume 76, Issue 1, pp 193–207 | Cite as

DYRK1B regulates Hedgehog-induced microtubule acetylation

  • Rajeev Singh
  • Philipp Simon Holz
  • Katrin Roth
  • Anna Hupfer
  • Wolfgang Meissner
  • Rolf Müller
  • Malte Buchholz
  • Thomas M. Gress
  • Hans-Peter Elsässer
  • Ralf Jacob
  • Matthias LauthEmail author
Original Article


The posttranslational modification (PTM) of tubulin subunits is important for the physiological functions of the microtubule (MT) cytoskeleton. Although major advances have been made in the identification of enzymes carrying out MT-PTMs, little knowledge is available on how intercellular signaling molecules and their associated pathways regulate MT-PTM-dependent processes inside signal-receiving cells. Here we show that Hedgehog (Hh) signaling, a paradigmatic intercellular signaling system, affects the MT acetylation state in mammalian cells. Mechanistically, Hh pathway activity increases the levels of the MT-associated DYRK1B kinase, resulting in the inhibition of GSK3β through phosphorylation of Serine 9 and the subsequent suppression of HDAC6 enzyme activity. Since HDAC6 represents a major tubulin deacetylase, its inhibition increases the levels of acetylated MTs. Through the activation of DYRK1B, Hh signaling facilitates MT-dependent processes such as intracellular mitochondrial transport, mesenchymal cell polarization or directed cell migration. Taken together, we provide evidence that intercellular communication through Hh signals can regulate the MT cytoskeleton and contribute to MT-dependent processes by affecting the level of tubulin acetylation.


Hedgehog SHH DYRK1B HDAC6 GSK3β Microtubules Acetylation Organelle transport Cell migration 



Dual specificity-regulated kinase 1B (a.k.a. MIRK)




Sonic Hedgehog


Glioma-associated oncogene 1


Glycogen synthase kinase 3 beta


Histone deacetylase 6




Acetylated α-tubulin


Smoothened agonist


Smoothened antagonist


Microtubule (MT) organizing center



This work was supported by grants obtained from the German Research Society (DFG-KFO325 and DFG-LA2829/9-1), the Behring-Röntgen Foundation and the University Hospital Giessen-Marburg (UKGM).

Compliance with ethical standards

Conflict of interest

No competing interest declared.

Supplementary material

18_2018_2942_MOESM1_ESM.pdf (1.5 mb)
Supplementary material 1 (PDF 1510 kb)


  1. 1.
    Aberger F, Ruiz IAA (2014) Context-dependent signal integration by the GLI code: the oncogenic load, pathways, modifiers and implications for cancer therapy. Semin Cell Dev Biol 33:93–104CrossRefGoogle Scholar
  2. 2.
    Akella JS, Wloga D, Kim J, Starostina NG, Lyons-Abbott S, Morrissette NS, Dougan ST, Kipreos ET, Gaertig J (2010) MEC-17 is an alpha-tubulin acetyltransferase. Nature 467:218–222CrossRefGoogle Scholar
  3. 3.
    Ashford AL, Oxley D, Kettle J, Hudson K, Guichard S, Cook SJ, Lochhead PA (2014) A novel DYRK1B inhibitor AZ191 demonstrates that DYRK1B acts independently of GSK3beta to phosphorylate cyclin D1 at Thr(286), not Thr(288). Biochem J 457:43–56CrossRefGoogle Scholar
  4. 4.
    Bacher CP, Reichenzeller M, Athale C, Herrmann H, Eils R (2004) 4-D single particle tracking of synthetic and proteinaceous microspheres reveals preferential movement of nuclear particles along chromatin—poor tracks. BMC Cell Biol 5:45CrossRefGoogle Scholar
  5. 5.
    Barakat MT, Humke EW, Scott MP (2010) Learning from Jekyll to control Hyde: Hedgehog signaling in development and cancer. Trends Mol Med 16:337–348CrossRefGoogle Scholar
  6. 6.
    Bijlsma MF, Borensztajn KS, Roelink H, Peppelenbosch MP, Spek CA (2007) Sonic hedgehog induces transcription-independent cytoskeletal rearrangement and migration regulated by arachidonate metabolites. Cell Signal 19:2596–2604CrossRefGoogle Scholar
  7. 7.
    Bijlsma MF, Damhofer H, Roelink H (2012) Hedgehog-stimulated chemotaxis is mediated by smoothened located outside the primary cilium. Sci Signal 5:ra60Google Scholar
  8. 8.
    Boyault C, Zhang Y, Fritah S, Caron C, Gilquin B, Kwon SH, Garrido C, Yao TP, Vourc’h C, Matthias P et al (2007) HDAC6 controls major cell response pathways to cytotoxic accumulation of protein aggregates. Genes Dev 21:2172–2181CrossRefGoogle Scholar
  9. 9.
    Briscoe J, Therond PP (2013) The mechanisms of Hedgehog signalling and its roles in development and disease. Nat Rev Mol Cell Biol 14:416–429CrossRefGoogle Scholar
  10. 10.
    Cai D, McEwen DP, Martens JR, Meyhofer E, Verhey KJ (2009) Single molecule imaging reveals differences in microtubule track selection between Kinesin motors. PLoS Biol 7:e1000216CrossRefGoogle Scholar
  11. 11.
    Chen JK, Taipale J, Young KE, Maiti T, Beachy PA (2002) Small molecule modulation of Smoothened activity. Proc Natl Acad Sci USA 99:14071–14076CrossRefGoogle Scholar
  12. 12.
    Chen PB, Hung JH, Hickman TL, Coles AH, Carey JF, Weng Z, Chu F, Fazzio TG (2013) Hdac6 regulates Tip60-p400 function in stem cells. Elife 2:e01557CrossRefGoogle Scholar
  13. 13.
    Chen S, Owens GC, Makarenkova H, Edelman DB (2010) HDAC6 regulates mitochondrial transport in hippocampal neurons. PLoS One 5:e10848CrossRefGoogle Scholar
  14. 14.
    Collins CS, Hong J, Sapinoso L, Zhou Y, Liu Z, Micklash K, Schultz PG, Hampton GM (2006) A small interfering RNA screen for modulators of tumor cell motility identifies MAP4K4 as a promigratory kinase. Proc Natl Acad Sci US A 103:3775–3780CrossRefGoogle Scholar
  15. 15.
    Dafinger C, Liebau MC, Elsayed SM, Hellenbroich Y, Boltshauser E, Korenke GC, Fabretti F, Janecke AR, Ebermann I, Nurnberg G et al (2011) Mutations in KIF7 link Joubert syndrome with Sonic Hedgehog signaling and microtubule dynamics. J Clin Invest 121:2662–2667CrossRefGoogle Scholar
  16. 16.
    de la Roche M, Ritter AT, Angus KL, Dinsmore C, Earnshaw CH, Reiter JF, Griffiths GM (2013) Hedgehog signaling controls T cell killing at the immunological synapse. Science 342:1247–1250CrossRefGoogle Scholar
  17. 17.
    Deng X, Ewton DZ, Li S, Naqvi A, Mercer SE, Landas S, Friedman E (2006) The kinase Mirk/Dyrk1B mediates cell survival in pancreatic ductal adenocarcinoma. Cancer Res 66:4149–4158CrossRefGoogle Scholar
  18. 18.
    Deribe YL, Wild P, Chandrashaker A, Curak J, Schmidt MH, Kalaidzidis Y, Milutinovic N, Kratchmarova I, Buerkle L, Fetchko MJ et al (2009) Regulation of epidermal growth factor receptor trafficking by lysine deacetylase HDAC6. Sci Signal 2:ra84Google Scholar
  19. 19.
    Desai SP, Bhatia SN, Toner M, Irimia D (2013) Mitochondrial localization and the persistent migration of epithelial cancer cells. Biophys J 104:2077–2088CrossRefGoogle Scholar
  20. 20.
    Dhanyamraju PK, Holz PS, Finkernagel F, Fendrich V, Lauth M (2014). Histone deacetylase 6 represents a novel drug target in the oncogenic Hedgehog signaling pathway. Mol Cancer Ther 14(3):727–39CrossRefGoogle Scholar
  21. 21.
    Dompierre JP, Godin JD, Charrin BC, Cordelieres FP, King SJ, Humbert S, Saudou F (2007) Histone deacetylase 6 inhibition compensates for the transport deficit in Huntington’s disease by increasing tubulin acetylation. J Neurosci 27:3571–3583CrossRefGoogle Scholar
  22. 22.
    Duchon A, Herault Y (2016) DYRK1A, a dosage-sensitive gene involved in neurodevelopmental disorders, is a target for drug development in Down syndrome. Front Behav Neurosci 10:104CrossRefGoogle Scholar
  23. 23.
    Etienne-Manneville S, Hall A (2003) Cdc42 regulates GSK-3beta and adenomatous polyposis coli to control cell polarity. Nature 421:753–756CrossRefGoogle Scholar
  24. 24.
    Friedman E (2013) Mirk/dyrk1B kinase in ovarian cancer. Int J Mol Sci 14:5560–5575CrossRefGoogle Scholar
  25. 25.
    Goetz SC, Anderson KV (2010) The primary cilium: a signalling centre during vertebrate development. Nat Rev Genet 11:331–344CrossRefGoogle Scholar
  26. 26.
    Gomes ER, Jani S, Gundersen GG (2005) Nuclear movement regulated by Cdc42, MRCK, myosin, and actin flow establishes MTOC polarization in migrating cells. Cell 121:451–463CrossRefGoogle Scholar
  27. 27.
    Gorojankina T (2016) Hedgehog signaling pathway: a novel model and molecular mechanisms of signal transduction. Cell Mol Life Sci 73(7):1317–32CrossRefGoogle Scholar
  28. 28.
    Goulimari P, Knieling H, Engel U, Grosse R (2008) LARG and mDia1 link Galpha12/13 to cell polarity and microtubule dynamics. Mol Biol Cell 19:30–40CrossRefGoogle Scholar
  29. 29.
    Gruber W, Hutzinger M, Elmer DP, Parigger T, Sternberg C, Cegielkowski L, Zaja M, Leban J, Michel S, Hamm S et al (2016) DYRK1B as therapeutic target in Hedgehog/GLI-dependent cancer cells with Smoothened inhibitor resistance. Oncotarget 7:7134–7148CrossRefGoogle Scholar
  30. 30.
    Hammond JW, Huang CF, Kaech S, Jacobson C, Banker G, Verhey KJ (2010) Posttranslational modifications of tubulin and the polarized transport of kinesin-1 in neurons. Mol Biol Cell 21:572–583CrossRefGoogle Scholar
  31. 31.
    Hickmott J (2015) DYRK1B variant linked to autosomal dominant metabolic syndrome. Clin Genet 87:30–31CrossRefGoogle Scholar
  32. 32.
    Hubbert C, Guardiola A, Shao R, Kawaguchi Y, Ito A, Nixon A, Yoshida M, Wang XF, Yao TP (2002) HDAC6 is a microtubule-associated deacetylase. Nature 417:455–458CrossRefGoogle Scholar
  33. 33.
    Hui CC, Angers S (2011) Gli proteins in development and disease. Annu Rev Cell Dev Biol 27:513–537CrossRefGoogle Scholar
  34. 34.
    Janke C (2014) The tubulin code: molecular components, readout mechanisms, and functions. J Cell Biol 206:461–472CrossRefGoogle Scholar
  35. 35.
    Janke C, Montagnac G (2017) Causes and consequences of microtubule acetylation. Curr Biol 27:R1287–R1292CrossRefGoogle Scholar
  36. 36.
    Jesnowski R, Furst D, Ringel J, Chen Y, Schrodel A, Kleeff J, Kolb A, Schareck WD, Lohr M (2005) Immortalization of pancreatic stellate cells as an in vitro model of pancreatic fibrosis: deactivation is induced by matrigel and N-acetylcysteine. Lab Invest 85:1276–1291CrossRefGoogle Scholar
  37. 37.
    Kawaguchi Y, Kovacs JJ, McLaurin A, Vance JM, Ito A, Yao TP (2003) The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell 115:727–738CrossRefGoogle Scholar
  38. 38.
    Keramati AR, Fathzadeh M, Go GW, Singh R, Choi M, Faramarzi S, Mane S, Kasaei M, Sarajzadeh-Fard K, Hwa J et al (2014) A form of the metabolic syndrome associated with mutations in DYRK1B. N Engl J Med 370:1909–1919CrossRefGoogle Scholar
  39. 39.
    Khatra H, Khan PP, Pattanayak S, Bhadra J, Rather B, Chakrabarti S, Saha T, Sinha S (2018) Hedgehog antagonist pyrimidine-indole hybrid molecule inhibits ciliogenesis through microtubule destabilisation. ChemBioChem 19:723–735CrossRefGoogle Scholar
  40. 40.
    Kwon S, Zhang Y, Matthias P (2007) The deacetylase HDAC6 is a novel critical component of stress granules involved in the stress response. Genes Dev 21:3381–3394CrossRefGoogle Scholar
  41. 41.
    Lauth M, Bergstrom A, Shimokawa T, Tostar U, Jin Q, Fendrich V, Guerra C, Barbacid M, Toftgard R (2010) DYRK1B-dependent autocrine-to-paracrine shift of Hedgehog signaling by mutant RAS. Nat Struct Mol Biol 17:718–725CrossRefGoogle Scholar
  42. 42.
    Lee H, Ko HW (2016) Ciliary smoothened-mediated noncanonical hedgehog signaling promotes tubulin acetylation. Biochem Biophys Res Commun 480:574–579CrossRefGoogle Scholar
  43. 43.
    Lee JJ, Rothenberg ME, Seeley ES, Zimdahl B, Kawano S, Lu WJ, Shin K, Sakata-Kato T, Chen JK, Diehn M et al (2016a). Control of inflammation by stromal Hedgehog pathway activation restrains colitis. Proc Natl Acad Sci USAGoogle Scholar
  44. 44.
    Lee RT, Zhao Z, Ingham PW (2016) Hedgehog signalling. Development 143:367–372CrossRefGoogle Scholar
  45. 45.
    Li R, Gundersen GG (2008) Beyond polymer polarity: how the cytoskeleton builds a polarized cell. Nat Rev Mol Cell Biol 9:860–873CrossRefGoogle Scholar
  46. 46.
    Li Y, Shin D, Kwon SH (2012) Histone deacetylase 6 plays a role as a distinct regulator of diverse cellular processes. FEBS J 280(3):775–93Google Scholar
  47. 47.
    Lipinski RJ, Bijlsma MF, Gipp JJ, Podhaizer DJ, Bushman W (2008) Establishment and characterization of immortalized Gli-null mouse embryonic fibroblast cell lines. BMC Cell Biol 9:49CrossRefGoogle Scholar
  48. 48.
    Magiera MM, Singh P, Gadadhar S, Janke C (2018) Tubulin posttranslational modifications and emerging links to human disease. Cell 173:1323–1327CrossRefGoogle Scholar
  49. 49.
    Mak AB, Nixon AM, Kittanakom S, Stewart JM, Chen GI, Curak J, Gingras AC, Mazitschek R, Neel BG, Stagljar I et al (2012) Regulation of CD133 by HDAC6 promotes beta-catenin signaling to suppress cancer cell differentiation. Cell Rep 2:951–963CrossRefGoogle Scholar
  50. 50.
    McGlinn E, Tabin CJ (2006) Mechanistic insight into how Shh patterns the vertebrate limb. Curr Opin Genet Dev 16:426–432CrossRefGoogle Scholar
  51. 51.
    Mercer SE, Friedman E (2006) Mirk/Dyrk1B: a multifunctional dual-specificity kinase involved in growth arrest, differentiation, and cell survival. Cell Biochem Biophys 45:303–315CrossRefGoogle Scholar
  52. 52.
    Mishra P, Chan DC (2016) Metabolic regulation of mitochondrial dynamics. J Cell Biol 212:379–387CrossRefGoogle Scholar
  53. 53.
    Montagnac G, Meas-Yedid V, Irondelle M, Castro-Castro A, Franco M, Shida T, Nachury MV, Benmerah A, Olivo-Marin JC, Chavrier P (2013) alphaTAT1 catalyses microtubule acetylation at clathrin-coated pits. Nature 502:567–570CrossRefGoogle Scholar
  54. 54.
    Nam HS, Benezra R (2009) High levels of Id1 expression define B1 type adult neural stem cells. Cell Stem Cell 5:515–526CrossRefGoogle Scholar
  55. 55.
    Pak E, Segal RA (2016) Hedgehog signal transduction: key players, oncogenic drivers, and cancer therapy. Dev Cell 38:333–344CrossRefGoogle Scholar
  56. 56.
    Polizio AH, Chinchilla P, Chen X, Kim S, Manning DR, Riobo NA (2011) Heterotrimeric Gi proteins link Hedgehog signaling to activation of Rho small GTPases to promote fibroblast migration. J Biol Chem 286:19589–19596CrossRefGoogle Scholar
  57. 57.
    Polizio AH, Chinchilla P, Chen X, Manning DR, Riobo NA (2011b) Sonic Hedgehog activates the GTPases Rac1 and RhoA in a Gli-independent manner through coupling of smoothened to Gi proteins. Sci Signal 4:pt7Google Scholar
  58. 58.
    Portran D, Schaedel L, Xu Z, Thery M, Nachury MV (2017) Tubulin acetylation protects long-lived microtubules against mechanical ageing. Nat Cell Biol 19:391–398CrossRefGoogle Scholar
  59. 59.
    Pugacheva EN, Jablonski SA, Hartman TR, Henske EP, Golemis EA (2007) HEF1-dependent Aurora A activation induces disassembly of the primary cilium. Cell 129:1351–1363CrossRefGoogle Scholar
  60. 60.
    Quintana A, Hoth M (2012) Mitochondrial dynamics and their impact on T cell function. Cell Calcium 52:57–63CrossRefGoogle Scholar
  61. 61.
    Reed NA, Cai D, Blasius TL, Jih GT, Meyhofer E, Gaertig J, Verhey KJ (2006) Microtubule acetylation promotes kinesin-1 binding and transport. Curr Biol 16:2166–2172CrossRefGoogle Scholar
  62. 62.
    Reiter JF, Leroux MR (2017) Genes and molecular pathways underpinning ciliopathies. Nat Rev Mol Cell Biol 18:533–547CrossRefGoogle Scholar
  63. 63.
    Robbins DJ, Fei DL, Riobo NA (2012) The hedgehog signal transduction network. Sci Signal 5:re6Google Scholar
  64. 64.
    Rohatgi R, Milenkovic L, Scott MP (2007) Patched1 regulates hedgehog signaling at the primary cilium. Science 317:372–376CrossRefGoogle Scholar
  65. 65.
    Sakai N, Tager AM (2013) Fibrosis of two: epithelial cell-fibroblast interactions in pulmonary fibrosis. Biochim Biophys Acta 1832:911–921CrossRefGoogle Scholar
  66. 66.
    Santo L, Hideshima T, Kung AL, Tseng JC, Tamang D, Yang M, Jarpe M, van Duzer JH, Mazitschek R, Ogier WC et al (2012) Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma. Blood 119:2579–2589CrossRefGoogle Scholar
  67. 67.
    Sasaki N, Kurisu J, Kengaku M (2010) Sonic hedgehog signaling regulates actin cytoskeleton via Tiam1-Rac1 cascade during spine formation. Mol Cell Neurosci 45(4):335-44CrossRefGoogle Scholar
  68. 68.
    Saxton WM, Hollenbeck PJ (2012) The axonal transport of mitochondria. J Cell Sci 125:2095–2104CrossRefGoogle Scholar
  69. 69.
    Schneider P, Miguel Bayo-Fina J, Singh R, Kumar Dhanyamraju P, Holz P, Baier A, Fendrich V, Ramaswamy A, Baumeister S, Martinez ED et al (2015) Identification of a novel actin-dependent signal transducing module allows for the targeted degradation of GLI1. Nat Commun 6:8023CrossRefGoogle Scholar
  70. 70.
    Shan B, Yao TP, Nguyen HT, Zhuo Y, Levy DR, Klingsberg RC, Tao H, Palmer ML, Holder KN, Lasky JA (2008) Requirement of HDAC6 for transforming growth factor-beta1-induced epithelial-mesenchymal transition. J Biol Chem 283:21065–21073CrossRefGoogle Scholar
  71. 71.
    Shin K, Lee J, Guo N, Kim J, Lim A, Qu L, Mysorekar IU, Beachy PA (2011) Hedgehog/Wnt feedback supports regenerative proliferation of epithelial stem cells in bladder. Nature 472:110–114CrossRefGoogle Scholar
  72. 72.
    Singh R, Dhanyamraju PK, Lauth M (2017) DYRK1B blocks canonical and promotes non-canonical Hedgehog signaling through activation of the mTOR/AKT pathway. Oncotarget 8:833–845Google Scholar
  73. 73.
    Song WJ, Song EA, Jung MS, Choi SH, Baik HH, Jin BK, Kim JH, Chung SH (2015) Phosphorylation and inactivation of glycogen synthase kinase 3beta (GSK3beta) by dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A). J Biol Chem 290:2321–2333CrossRefGoogle Scholar
  74. 74.
    Stambolic V, Woodgett JR (1994) Mitogen inactivation of glycogen synthase kinase-3 beta in intact cells via serine 9 phosphorylation. Biochem J 303(Pt 3):701–704CrossRefGoogle Scholar
  75. 75.
    Sun W, Qureshi HY, Cafferty PW, Sobue K, Agarwal-Mawal A, Neufield KD, Paudel HK (2002) Glycogen synthase kinase-3beta is complexed with tau protein in brain microtubules. J Biol Chem 277:11933–11940CrossRefGoogle Scholar
  76. 76.
    Tariki M, Dhanyamraju PK, Fendrich V, Borggrefe T, Feldmann G, Lauth M (2014) The Yes-associated protein controls the cell density regulation of Hedgehog signaling. Oncogenesis 3:e112CrossRefGoogle Scholar
  77. 77.
    Tariki M, Wieczorek SA, Schneider P, Banfer S, Veitinger S, Jacob R, Fendrich V, Lauth M (2013) RIO kinase 3 acts as a SUFU-dependent positive regulator of Hedgehog signaling. Cell Signal 25:2668–2675CrossRefGoogle Scholar
  78. 78.
    Walter WJ, Beranek V, Fischermeier E, Diez S (2012) Tubulin acetylation alone does not affect kinesin-1 velocity and run length in vitro. PLoS ONE 7:e42218CrossRefGoogle Scholar
  79. 79.
    Wang B, Rao YH, Inoue M, Hao R, Lai CH, Chen D, McDonald SL, Choi MC, Wang Q, Shinohara ML et al (2014) Microtubule acetylation amplifies p38 kinase signalling and anti-inflammatory IL-10 production. Nat Commun 5:3479CrossRefGoogle Scholar
  80. 80.
    Westermann S, Weber K (2003) Posttranslational modifications regulate microtubule function. Nat Rev Mol Cell Biol 4:938–947CrossRefGoogle Scholar
  81. 81.
    Xu Z, Schaedel L, Portran D, Aguilar A, Gaillard J, Marinkovich MP, Thery M, Nachury MV (2017) Microtubules acquire resistance from mechanical breakage through intralumenal acetylation. Science 356:328–332CrossRefGoogle Scholar
  82. 82.
    Yan J (2014) Interplay between HDAC6 and its interacting partners: essential roles in the aggresome-autophagy pathway and neurodegenerative diseases. DNA Cell Biol 33:567–580CrossRefGoogle Scholar
  83. 83.
    Zhang Y, Kwon S, Yamaguchi T, Cubizolles F, Rousseaux S, Kneissel M, Cao C, Li N, Cheng HL, Chua K et al (2008) Mice lacking histone deacetylase 6 have hyperacetylated tubulin but are viable and develop normally. Mol Cell Biol 28:1688–1701CrossRefGoogle Scholar
  84. 84.
    Zilberman Y, Ballestrem C, Carramusa L, Mazitschek R, Khochbin S, Bershadsky A (2009) Regulation of microtubule dynamics by inhibition of the tubulin deacetylase HDAC6. J Cell Sci 122:3531–3541CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Rajeev Singh
    • 1
  • Philipp Simon Holz
    • 1
  • Katrin Roth
    • 2
  • Anna Hupfer
    • 1
  • Wolfgang Meissner
    • 1
  • Rolf Müller
    • 1
  • Malte Buchholz
    • 3
  • Thomas M. Gress
    • 3
  • Hans-Peter Elsässer
    • 4
  • Ralf Jacob
    • 4
  • Matthias Lauth
    • 1
    Email author
  1. 1.Institute of Molecular Biology and Tumor Research (IMT), Center for Tumor- and Immune Biology (ZTI)Philipps UniversityMarburgGermany
  2. 2.Imaging Core Facility, Center for Tumor- and Immune Biology (ZTI)Philipps UniversityMarburgGermany
  3. 3.Clinic for Gastroenterology, Endocrinology, Metabolism and InfectiologyPhilipps UniversityMarburgGermany
  4. 4.Institute of Cytobiology and CytopathologyPhilipps UniversityMarburgGermany

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