Cell Biology

Recent reports published by the World Health Organization (WHO) entitled "The Global Burden of Disease" (GBD) highlights the importance of research on host-pathogen interactions. Evolution is an ongoing process driving the development of highly virulent and multi-resistant bacteria strains or so called “emerging pathogens“. A deeper understanding of the complex interaction between pathogenic bacteria and their host is inevitable to face these problems in the future. As Cell biologists, we address host-pathogen interaction on the level of single cells, embodying the smallest living unit on both sides. Upon contact, pathogens need to manipulate the normal behavior of host cells in order to establish a niche for survival and to evade the hosts defense mechanisms. We study these induced changes on the cellular and molecular level, in order to exactly understand which host process is targeted by a given virulence mechanism an why.

Leader

Selected Publications

Stradal TE, Courtney KD, Rottner K, Hahne P, Small JV, Pendergast AM (2001) The Abl interactor proteins localize to sites of actin polymerization at the tips of lamellipodia and filopodia. Curr Biol 11: 891-895.

Steffen A, Rottner K, Ehinger J, Innocenti M, Scita G, Wehland J, Stradal TE (2004) Sra-1 and Nap1 link Rac to actin assembly driving lamellipodia formation. EMBO J 23: 749-759.

Disanza A, Mantoani S, Hertzog M, Gerboth S, Frittoli E, Steffen A, Berhoerster K, Kreienkamp HJ, Milanesi F, Di Fiore PP, Ciliberto A, Stradal TE, Scita G (2006) Regulation of cell shape by Cdc42 is mediated by the synergic actin bundling activity of the Eps8:IRSp53 complex. Nat Cell Biol 8: 1337-1347. 

Weiss SM, Ladwein M, Schmidt D, Ehinger J, Lommel S, Städing K, Beutling U, Disanza A, Frank R, Jänsch L, Scita G, Gunzer F, Rottner K, Stradal TE (2009) IRSp53 links Tir to EspFU/N-WASP-mediated actin assembly in EHEC pedestal formation. Cell Host Microbe 5: 244-258.

Hänisch J, Kölm R, Wozniczka M, Bumann D, Rottner K, Stradal TE (2011) Activation of a RhoA/myosin II-dependent but Arp2/3 complex-independent pathway facilitates Salmonella invasion. Cell Host Microbe 9: 273-285.

Publications

Research articles

Schnoor M, Stradal TE, Rottner K. (2018) Cortactin: Cell Functions of A Multifaceted Actin-Binding Protein. Trends Cell Biol28(2):79-98. doi: 10.1016/j.tcb.2017.10.009.

Böttcher RT, Veelders M, Rombaut P, Faix J, Theodosiou M, Stradal TE, Rottner K, Zent R, Herzog F, Fässler R. (2017) Kindlin-2 recruits paxillin and Arp2/3 to promote membrane protrusions during initial cell spreading. J Cell Biol216(11):3785-3798. doi: 10.1083/jcb.201701176.

Litschko C, Linkner J, Brühmann S, Stradal TEB, Reinl T, Jänsch L, Rottner K, Faix J. (2017) Differential functions of WAVE regulatory complex subunits in the regulation of actin-driven processes. Eur J Cell Biol96(8):715-727. oi: 10.1016/j.ejcb.2017.08.003.

Kage F, Steffen A, Ellinger A, Ranftler C, Gehre C, Brakebusch C, Pavelka M, Stradal T, Rottner K. (2017) FMNL2 and -3 regulate Golgi architecture and anterograde transport downstream of Cdc42. Sci Rep7(1):9791. doi:10.1038/s41598-017-09952-1.

Noumeur SR, Helaly SE, Jansen R, Gereke M, Stradal TEB, Harzallah D, Stadler M. (2017) Preussilides A-F, Bicyclic Polyketides from the Endophytic Fungus Preussia similis with Antiproliferative Activity. J Nat Prod.;80(5):1531-1540. doi: 10.1021/acs.jnatprod.7b00064.

Kage F, Winterhoff M, Dimchev V, Mueller J, Thalheim T, Freise A, Brühmann S, Kollasser J, Block J, Dimchev G, Geyer M, Schnittler HJ, Brakebusch C, Stradal TE, Carlier MF, Sixt M, Käs J, Faix J, Rottner (2017) FMNL formins boost lamellipodial force generation. Nat Commun.;8:14832. doi: 10.1038/ncomms14832.

Horstmann JA, Zschieschang E, Truschel T, de Diego J, Lunelli M, Rohde M, May T, Strowig T, Stradal T, Kolbe M, Erhardt M. (2017) Flagellin phase-dependent swimming on epithelial cell surfaces contributes to productive Salmonella gut colonisation. Cell Microbiol.  doi: 10.1111/cmi.12739.

Leithner A, Eichner A, Müller J, Reversat A, Brown M, Schwarz J, Merrin J, de Gorter DJ, Schur F, Bayerl J, de Vries I, Wieser S, Hauschild R, Lai FP, Moser M, Kerjaschki D, Rottner K, Small JV, Stradal TE, Sixt M. (2016) Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes. Nat Cell Biol18(11):1253-1259. doi: 10.1038/ncb3426.

Thiam HR, Vargas P, Carpi N, Crespo CL, Raab M, Terriac E, King MC, Jacobelli J, Alberts AS, Stradal T, Lennon-Dumenil AM, Piel M. Perinuclear Arp2/3-driven actin polymerization enables nuclear deformation to facilitate cell migration through complex environments. Nat Commun. 2016 Mar 15;7:10997.

Rottner K, Stradal TEHow distinct Arp2/3 complex variants regulate actin filament assembly. Nat Cell Biol. 2015 Dec 23;18(1):1-3.

Blasche, S., Arens, S., Ceol, A., Siszler, G., Schmidt, M.A., Häuser, R., Schwarz, F., Wuchty, S., Aloy, P., Uetz, P., Stradal, T.E., Kögl, M. (2014) The EHEC-host interactome reveals novel targets for the translocated intimin receptorSci Rep. 18(4), 7531.

Schlüter K, Waschbüsch D, Anft M, Hügging D, Kind S, Hänisch J, Lakisic G, Gautreau A, Barnekow A, Stradal TE. (2014) JMY is involved in anterograde vesicle trafficking from the trans-Golgi networkEur. J. Cell Biol. 93(5-6), 194-204.

Steffen A., Ladwein M., Dimchev G.A., HeinA., Schwenkmezger L., Arens S., Ladwein K.I., Holleboom J.M., Schur F., Small J.V., Schwarz J., Gerhard R., Faix J., Stradal T.E., Brakebusch C., and Rottner K. (2013) Rac function is critical for cell migration but not required for spreading and focal adhesion formationJ. Cell Sci. 126(20), 4572-88.

Koestler S., Steffen A., Nemethova M., Winterhoff M., Luo N., Holleboom J.M., Krupp J., Jacob S., Vinzenz M., Schur F., Schlueter K., Gunning P., Winkler C., Schmeiser C., Faix J., Stradal T.E., Small J.V., Rottner K. (2013) Arp2/3 complex is essential for actin network treadmilling as well as for targeting of capping protein and cofilinMol. Biol. Cell 24(18), 2861-75.

Block, J., Breitsprecher, D., Kühn, S., Winterhoff, M., Kage, F., Geffers, R., Duwe, P., Rohn, J.L., Baum, B., Brakebusch, C., Geyer, M., Stradal, T.E., Faix, J., Rottner, K. (2012) FMNL2 drives actin-based protrusion and migration downstream of Cdc42Curr. Biol.22, (11), 1005-1012

Hänisch, J., Stradal, T.E., Rottner, K (2012) A novel contractility pathway operating in Salmonella invasionVirulence 3(1), 81-86.

de Groot, J.C., Schlüter, K., Carius, Y., Quedenau, C., Vingadassalom, D., Faix, J., Weiss, S.M., Reichelt, J., Standfuß-Gabisch, C., Lesser, C.F., Leong, J.M., Heinz, D.W., Büssow, K., Stradal, T.E. (2011) Structural basis for complex formation between human IRSp53 and the translocated intemin receptor Tir of enterohemorrhagic E. coliStructure 19(9), 1294-1306.

Linkner, J., Witte, G., Stradal, T.E., Curth, U., Faix, J. (2011) High-Resolution X-Ray Structure of the Trimeric Scar/WAVE-Complex Precursor Brk1PLoS One 6(6), e21327. 

Oelkers, J.M., Vinzenz, M., Nemethova, M., Jacob, S., Lai, F.P., Block, J., Szczodrak, M., Kerkhoff, E., Backert, S., Schlüter, K., Stradal, T.E., Small, J.V., Koestler, S.A., Rottner, K. (2011) Microtubules as platforms for assaying actin polymerization in vivoPLoS One 6(5), e19931. 

Kabaso, D., Shlomovitz, R., Schloen, K., Stradal, T.E., Gov, N.S. (2011) Theoretical model for cellular shapes driven by protrusive and adhesive forcesPLoS Comput. Biol. 7(5), e1001127. 

Dubielecka, P.M., Ladwein, K.I., Xiong, X., Migeotte, I., Chorzalska, A., Anderson, K.V., Sawicki, J.A., Rottner, K., Stradal, T.E., Kotula L. (2011) Essential role for Abi1 in embryonic survival and WAVE2 complex integrityProc. Natl. Acad. Sci. USA 108(17), 7022-7027. 

Hänisch, J., Kölm, R., Wozniczka, M., Bumann, D. Rottner, K, Stradal, T.E. (2011) Activation of a RhoA/myosin II-dependent but Arp2/3 complex-independent pathway facilitates Salmonella invasionCell Host & Microbe 9(4), 273-285.

Breitsprecher, D., Kiesewetter, A.K., Linkner, J., Vinzenz, M., Stradal, T.E., Small, J.V., Curth, U., Dickinson, R.B., Faix, J. (2011) Molecular mechanism of Ena/VASP-mediated actin-filament elongationEMBO J. 30(3), 456-467. 

Klink, B.U., Barden, S., Heidler, T.V., Borchers, C., Ladwein, M., Stradal, T.E., Rottner, K., Heinz, D.W. (2010) Structure of Shigella IpgB2 in complex with human RhoA: implications for the mechanism of bacterial guanine nucleotide exchange factor mimicryJ. Biol. Chem. 285(22), 17197-17208. 

Tahirovic, S., Hellal, F., Neukirchen, D., Hindges, R., Garvalov, B., Flynn, K., Stradal, T.E., Chrostek-Grashoff, A., Brakebusch, C., Bradke, F. (2010) Rac1 regulates neuronal polarization through the WAVE-complex. J. Neurosci. 30(20), 6930-6943.

Horn, J., Wang,, X., Reichardt, P., Maltzman, J., Stradal, T.E., Breitling, D., Warnecke, N., Simeoni, L., Gunzer, M., Yablonski, D., Koretzky, G.A., Schraven B., Kliche, S. (2009) SLP76 is mandatory for TCR-mediated inside-out-signaling, but dispensable for CXCR4-mediated LFA-1 activation, adhesion and migration of T-cellsJ. Immunol. 183(9), 5756-5767.

Giuliani, C., Troglio, F., Zucconi, A., Malabarba, G.M., Stradal, T.E., Bai, Z., Cassata, G., Confalonieri, S., Chen, E., Hardin J.D., Soto M.C., Grant B.D., Scita, G. (2009) The F-BAR-containing TOCA family proteins coordinate N-WASP- and WAVE-dependent actin dynamics with membrane trafficking in C. elegans and mammalian cellsPLOS Genetics 5(10), e1000675. 

Hänisch, J., Ehinger, J., Ladwein, M., Rohde, M., Bosse, T., Steffen, A., Bumann, D., Misselwitz, B., Freihofer, P., Hardt, W.D., Stradal, T.E., Rottner, K. (2009) Molecular dissection of Salmonella-induced membrane ruffling versus invasionCell. Microbio. 12(1), 84-98. 

Lai, F.P., Szczodrak, M., Ladwein, M., Acconcia, F., Benesch, S., Auinger, S., Faix, J. Small, J.V., Polo, S., Stradal, T.E., Rottner, K. (2009) Cortactin Promotes Migration and PDGF-induced Actin Reorganization by Signaling to RacMol. Biol. Cell 20(14), 3209-3223. 

Weiss, S.M., Ladwein, M., Schmidt, D., Ehinger, J., Lommel, S., Städing, K., Beutling, U., Disanza, A., Frank, R., Jänsch, L., Scita, G., Gunzer, F., Rottner, K., Stradal, T.E. (2009) IRSp53 links Tir to EspFU/N-WASP-mediated actin assembly in EHEC pedestal formationCell Host & Microbe 5, 244-258. 

Block, J., Stradal, T.E., Hänisch, J., Geffers, R., Köstler, S., Urban, E., Small, J.V., Rottner, K., Faix, J. (2008). Filopodia formation induced by active Dia2/Drf3J. Microsc. 231(3), 506-517. 

Beutling, U., Städing, K., Stradal, T.E., Frank, R. (2008) Large-Scale Analysis of Protein-Protein Interactions Using Cellulose-Bound Peptide ArraysAdv. Biochem. Eng. Biotechnol. 110, 115-152.

Derivery, E., Fink, J., Martin, D., Houdusse, A., Piel, M., Stradal, T.E., Louvard, D., Gautreau A. (2008) Free Brick1 is a trimeric precursor in the assembly of a functional WAVE-complexPLoS ONE 3(6), e2462. 

Lai, F.P., Szczodrak, M., Block, J., Faix, J., Breitsprecher, D., Mannherz, H.G., Stradal, T.E., Dunn, G.A., Small, J.V., Rottner, K. (2008) Arp2/3 complex interactions and actin network turnover in lamellipodiaEMBO J. 27(7), 982-992.

Bosse T., Ehinger J., Czuchra A., Benesch S., Steffen A., Wu X., Schloen K., Niemann H.H., Scita G., Stradal, T.E., Brakebusch, C., Rottner, K. (2007) Cdc42 and PI3K drive Rac-mediated actin polymerization downstream of c-Met in distinct and common pathwaysMol. Cell. Biol. 27(19), 6615-6628.

Menasche, G., Kliche, S., Chen, E.J., Stradal, T.E., Schraven, B., Koretzky, G. (2007) RIAM links the ADAP/SKAP-55 signaling module to Rap1, facilitating T-cell-receptor-mediated integrin activationMol. Cell. Biol. 27(11), 4070-4081. 

Chmielowiec, J., Borowiak, M., Morkel, M., Stradal, T.E., Munz, B., Werner, S., Wehland, J., Birchmeier, C., Birchmeier, W. (2007) c-Met is essential for wound healing in the skin. J. Cell Biol. 177(1), 151-162. 

Disanza A., Mantoani S., Hertzog M., Gerboth S., Frittoli E., Steffen A., Berhoerster K., Kreienkamp H.J., Milanesi F., Di Fiore P.P., Ciliberto A., Stradal, T.E., Scita G. (2006) Regulation of cell shape by Cdc42 is mediated by the synergic actin bundling activity of the Eps8:IRSp53 complexNat. Cell Biol. 8, 1337-1347. 

Steffen, A., Faix, J., Resch, G.P., Linkner, J., Wehland, J., Small, J.V., Rottner, K., Stradal, T.E. (2006) Filopodia formation in the absence of functional WAVE- and Arp2/3-complexesMol. Biol. Cell 17(6), 2581-2591. 

Frese, S., Schubert, W.D., Findeis, A.C., Marquardt, T., Roske, Y.S., Stradal, T.E., Heinz, D.W. (2006) The phosphotyrosine peptide binding specificity of Nck1 and Nck2 Src homology 2 domains. J. Biol. Chem. 281(26), 18236-18245. 

Schirenbeck, A., Arasada, R., Bretschneider, T., Stradal, T.E., Schleicher, M., Faix, J. (2006) The bundling activity of vasodilator-stimulated phosphoprotein is required for filopodium formationProc. Natl. Acad. Sci. USA 103(20), 7694-7699. 

Innocenti, M., Gerboth, S., Rottner, K., Lai, F.P., Stradal, T.E., Frittoli, E., Didry, D., Polo, S., Disanza, A., Di Fiore, P.P., Carlier, M.F., Scita, G. (2005) Abi1 regulates the activity of N-WASP and WAVE in distinct actin-based processesNat. Cell Biol. 7, 969-976.

Benesch, S., Polo, S., Lai, F.P., Anderson, K.I., Stradal, T.E., Wehland, J., Rottner, K. (2005) N-WASP deficiency impairs EGF internalization and actin assembly at clathrin coated pitsJ. Cell Sci. 118, 3103-3115.

Dubois, T., Paléotti, O., Mironov, A.A., Fraisier, V., Stradal, T.E., De Matteis, M.A., Franco, M., Chavrier, P. (2005) ARHGAP10, a novel Golgi-localized GAP for Cdc42 that functions downstream of ARF1 to control Arp2/3 complex/F-actin dynamicsNat. Cell Biol. 7, 353-364. 

Chandrasekar, I., Stradal, T.E., Holt, M.R., Entschladen, F., Jockusch, B.M., Ziegler W.H. (2005) Vinculin acts as a sensor in lipid regulation of adhesion site turnover. J. Cell Sci. 118, 1461-1472. 

Jenzora, A., Behrendt, B.,Small, J.V., Wehland, J., and Stradal, T.E. (2005) PREL1 links Ras signalling to actin remodelling via Ena/VASP proteinsFEBS Lett. 579, 455–463.

Disanza, A., Carlier, M.F., Stradal, T.E., Didry, D., Frittoli, E., Confalonieri, S., Croce, A., Wehland, J., Di Fiore, P.P., Scita, G. (2004) Eps8 controls actin-based motility by capping the barbed ends of actin filamentsNat. Cell Biol. 6, 1180-1188. 

Pacholsky, D., Himmel, M., Löw, T., Stradal, T.E., Rottner, K., Fürst, D.O., van der Ven, P.F. (2004) Xin repeats define a novel actin binding motif. J. Cell Sci. 117, 5257-5268. 

Innocenti, M., Zucconi, A., Disanza, A., Frittoli, E., Areces, L.B., Steffen, A., Stradal, T.E., Di Fiore, P.P., Carlier, M.F., Scita, G. (2004) Abi1 is essential for the formation and activation of a WAVE2 signalling complexNat. Cell Biol6, 319-327.

Steffen, A., Rottner, K., Ehinger, J., Innocenti, M., Scita, G., Wehland, J., Stradal, T.E. (2004) Sra-1 and Nap1 link Rac to actin assembly driving lamellipodia formation. EMBO J. 23, 749-759.

Kaverina, I.N., Stradal, T.E., Gimona, M. (2003) Podosome formation in cultured A7r5 vascular smooth muscle cells requires Arp2/3-dependent de-novo actin polymerization at discrete microdomains J. Cell Sci. 116, 4915-4924. 

Benesch, S., Lommel, S., Steffen, A., Stradal, T.E., Scaplehorn, N., Way, M., Wehland, J., Rottner, K. (2002) Phosphatidylinositol 4,5-biphosphate (PIP2)-induced vesicle movement depends on N-WASP and involves Nck, WIP, and Grb2J. Biol. Chem. 277, 37771-37776.

Stradal, T.E., Courtney, K.D., Rottner, K., Hahne, P., Small, J.V., Pendergast, A.M. (2001) The Abl interactor proteins localize to sites of actin polymerization at the tips of lamellipodia and filopodiaCurr. Biol. 11, 891-895.

Stradal, T.E., Troxler, H., Heizmann, C.W., Gimona, M. (2000) Mapping the zinc ligands of S100A2 by site-directed mutagenesisJ. Biol. Chem275, 13219-13227.

Stradal, T.E., Gimona, M. (1999) Ca2+-dependent association of S100A6 (Calcyclin) with the plasma membrane and the nuclear envelope. J. Biol. Chem. 274, 31593-31596.

Review articles

Stradal TE, Costa SC. (2017) Type III Secreted Virulence Factors Manipulating Signaling to Actin Dynamics. Curr Top Microbiol Immunol399:175-199. doi: 10.1007/82_2016_35.

Rottner K, Stradal TE. (2016) How distinct Arp2/3 complex variants regulate actin filament assembly. Nat Cell Biol.;18(1):1-3.

Rottner, K., Stradal, T.E. (2011) Actin dynamics and turnover in cell motilityCurr. Opin. Cell. Biol. 23(5), 569-578. 

Rottner, K., Stradal, T.E. (2009) Poxviruses taking a ride on actin: new users of known hardwareCell Host & Microbe 6(6), 497-499. 

Faix, J., Breitsprecher, D., Stradal, T.E., Rottner, K. (2009) Filopodia: Complex models for simple rodsInt. J. Biochem. Cell Biol. 41(8-9), 1656-1664.

Stradal, T.E., Scita, G. (2006) Protein complexes regulating cellular actin assemblyCurr. Op. Cell Biol. 18, 4-10. 

Rottner, K., Stradal, T.E., Wehland, J. (2005) Bacteria – host cell interactions at the plasma membrane: stories on actin cytoskeleton subversionDev. Cell 9, 3-17.

Rottner, K., Lommel, S., Wehland, J., Stradal, T.E. (2004) Pathogen-induced actin filament rearrangement in infectious diseasesJ. Pathol. 204, 396-406. 

Stradal, T.E., Rottner, K., Disanza, A., Innocenti, M., Confalonieri, S., Scita, G. (2004). Regulation of actin dynamics by WASP and WAVE family proteinsTrends Cell Biol14, 303-311.

Small, J.V., Stradal, T.E., Vignal, E., Rottner, K. (2002) The lamellipodium: where motility beginsTrends Cell Biol. 12, 112-120. 

Stradal, T.E., Kranewitter, W., Winder, S.J., Gimona, M. (1998) CH domains revisitedFEBS Lett. 431, 134-137. 

Book contributions

Steffen, A., Stradal, T.E., Rottner, K. (2016) Signalling pathways controlling cellular actin organization. The Actin Cytoskelton in “Handbook of Experimental Pharmacology” (ed. B. Jockusch) Springer Books (in press)

Stradal, T.E., Pusch, R., Kliche, S. (2006) Molecular regulation of cytoskeletal rearrangements during T cell signalling. In: Results and Problems in Cell Differentiation (RPCD); Volume: Cell Communication in Nervous and Immune System (eds. B. Schraven & E. Gundelfinger), Springer Verlag, Berlin, 43, pp219-244.

Rottner, K., Kaverina, I.N., Stradal, T.E. (2006) Cytoskeleton proteins. In “Cell Biology: A Laboratory Handbook”, 3rd Edition (ed. J.E. Celis), Academic Press, pp111-119.

Stradal, T.E., Lommel, S., Wehland, J., Rottner, K. (2005) Host-pathogen interactions and Cell Motility: Learning from Bacteria. In “Cell Migration in Development and Disease” (ed. D. Wedlich), WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim, pp205-248.

Stradal, T.E., Sechi, A.S., Wehland, J., Rottner, K. (2003) The Cytoskeleton. In “Essential Cell Biology, Vol 1, ‘Cell Structure’: Practical Approach Series” (eds. M. Davey & M. Lord), Oxford University Press, pp365-389.

Other

Stradal, T.E., Backert, S. (2010) Host-pathogen interaction: How EHEC influence the actin cytoskeleton of the host cell. BioSpektrum 16 (6), 624-627.

Stradal, T.E. (2008) The regulation of cellular protrusions. Zellbiologie Aktuell 34(1), 17-22. 

Stradal, T.E., Wehland, J. (2005) Aktindynamik und WASP/WAVE-Proteine. BioSpektrum 11(3), 283-286.

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