2026/11/10(Tue) 11:00 -12:30 五樓第一會議室 5F, 1st Meeting Room
Title
Molecular orchestration of global actin remodelling by the formin INF2
Speaker
Dr. Roland Wedlich-Söldner (University of Münster)Abstract
The actin cytoskeleton rapidly reorganizes in response to intracellular calcium signals, driving cellular morphogenesis and wound healing. Among actin regulators, the formin INF2 uniquely mediates the “Calcium-mediated Actin Reset” (CaAR) reaction, orchestrating transient and global actin remodeling upon calcium influx. Excessive INF2 activity is linked to kidney and neuronal diseases, underscoring the need for its tight control. Combining live cell imaging with single molecule tracking, biochemistry and structural analysis we discover that INF2activity is tightly controlled by two interlinked mechanisms: canonical intramolecular autoinhibition and binding of the INF2 N-terminus to the side of actin filaments. Side-binding limits actin elongation and supports re-establishment of autoinhibition. Disruption of this negative feedback prolongs INF2 activity, affecting plasma membrane organization and repair as well as transcriptional control. Our findings uncover a novel product-inhibition mechanism that limits INF2 function and offer important insight into disease mechanisms linked to actin dysregulation.
CV:
Roland Wedlich-Söldner studied Biology in Munich and graduated with Regine Kahmann and Gero Steinberg on microtubule-dependent transport in the plant pathogenic fungus Ustilago maydis. During his postdoc with Rong Li at Harvard Medical school he studied the mechanisms of spontaneous cell polarization. He then headed a research group on “Cellular Dynamics and Cell patterning” at the Max Planck Institute of Biochemistry before joining the University of Münster in 2014 as professor and director of the Institute of Cell Dynamics and Imaging. His group uses high resolution life cell microscopy to identify fundamental concepts of cellular organization, with a focus on membrane organization and cytoskeletal dynamics.
Key publications:
[1]Haase D, Rasch C, Keller U, Tsytsyura Y, Glyvuk N, Elting A, Wittmar J, Janning A, Kahms M, Wedlich N, Schuberth C, Heuer A, Klingauf J, Wedlich-Soldner R. (2023) Tetraspanner-based nanodomains modulate BAR domain-induced membrane curvature. EMBO Rep, e57232.
[2]Bayraktar, S., Nehrig, J.#, Menis, E., Karli, K., Janning, A., Struk, T., Halbritter, J., Michgehl, U., Krahn, M.P., Schuberth, C.E.*, Pavenstädt, H.*, Wedlich-Söldner, R.* (2020) A deregulated stress response underlies distinct INF2 associated disease profiles. JASN 31, 1296-1313.
[3]Busto, J.V., Elting, A., Haase, D., Spira, F., Kuhlman, J., Schäfer-Herte, M. and Wedlich-Soldner, R. (2018) Lateral plasma membrane compartmentalization links protein function and turnover. EMBO J 37, pii: e99473.
[4]Wales, P., Schuberth, C.E., Aufschnaiter, R., Fels, J., García-Aguilar, I., Janning, A., Dlugos, C.P., Schäfer-Herte, M., Klingner, C., Wälte, M., Kuhlmann, J., Menis, E., Hockaday Kang, L., Maier, K.C., Hou, W., Russo, A., Higgs, H.N., Pavenstädt, H., Vogl, T., Roth, J., Qualmann, B., Kessels, M.M., Martin, D.E., Mulder, B. and Wedlich-Söldner, R. (2016). Calcium-mediated actin reset (CaAR) mediates acute cell adaptations. Elife 5, e19850.
[5]Klingner, C., Cherian, A.V., Fels, J., Diesinger, P.M., Aufschnaiter, R., Maghelli, N., Keil, T., Beck, G., Toliü-Nørrelykke, I.M., Bathe, M. and Wedlich-Soldner, R. (2014). Isotropic acto-myosin dynamics promote organization of the apical cell cortex in epithelial cells. J Cell Biol. 207, 107-21.
[6]Freisinger, T. Klünder, B., Johnson, J., Müller, N., Pichler, G., Beck, G., Costanzo, M., Boone, C., Cerione, R. A., Frey, E. and Wedlich-Soldner, R. (2013). Establishment of a robust single axis of cell polarity by coupling multiple positive feedback loops. Nat Commun 4, 1807.
[7]Spira, F., Mueller, N.S., Beck, G., von Olshausen, P., Beig, J., Wedlich-Soldner, R. (2012). Patchwork organization of the yeast plasma membrane into numerous coexisting domains. Nat Cell Biol 14, 640-8.
[8]Domínguez-Escobar, J., Chastanet, A., Crevenna, A. H., Fromion, V., *Wedlich-Soldner, R. and *Carballido-López, R. (2011). Processive Movement of MreB-Associated Cell Wall Biosynthetic Complexes in Bacteria. Science 333, 225-8. * shared corresp. authors.
[9]Riedl, J., Crevenna, A.H., Kessenbrock, K., Yu, J.H., Neukirchen, D., Bista, M., Bradke, F., Jenne, D., Holak, T.A., Werb, Z., Sixt, M. and Wedlich-Soldner, R. (2008). Lifeact - a versatile marker for the visualization of F-actin. Nature Methods 5, 605-7.
Language
演講語言 (Language): in English