Arbeitsgruppe Prof. Dr. Robert Grosse
am Pharmakologischen Institut der Philipps-Universität Marburg
Cytoskeletal Signaling
Dynamic rearrangement of the cytoskeleton regulates responses to a variety of extracellular signals that allow cells to move or to change shape. In the past few years substantial progress has been made in understanding some of the principal biochemical reactions and molecules responsible for actin filament growth and structure. These dynamic cytoskeletal rearrangements are controlled by defined signaling pathways, which orchestrate the activity of distinct actin nucleation factors. Only very recently we know that there are over 29 actin nucleators in humans, most of them with unknown physiological and pathophysiological functions, a list that is likely to expand in the near future. One large family of catalytically potent actin nucleators consists of the 15 highly conserved formin homology (FH) domain containing proteins, which are regulated through physical interactions with Rho-GTPases. We study novel regulatory interactions with formins to dissect their specific signaling functions and physiological roles in various cell motility processes such as cancer cell invasion or polarized cell movement during wound healing. In addition, many formins govern transcriptional activity of SRF through their effects on actin polymerization. One focus of our lab is to understand the synergistic link between formin-induced cytoskeletal dynamics and transcriptional output, which have substantial implications for cancer cell invasion and metastasis.
recent key papers:
Nürnberg A., Kitzing T., and Grosse R. (2011) Nucleating actin for invasion.
Nat Rev Cancer 11:177-187
Baarlink C., Brandt D., and Grosse R. (2010) SnapShot: Formins.
Brandt D.T., Baarlink C., Kitzing T.M., Kremmer E., Ivaska J., Nollau, P., Grosse R. (2009) SCAI acts as a suppressor of cancer cell invasion through the transcriptional control of beta1-integrin.
Goulimari P., Knieling H., Engel U., Grosse R. (2008) LARG and mDia1 link G12/13 to cell polarity and microtubule dynamics.
Kitzing T., Sahadevan A.S., Brandt D.T., Knieling H., Hannemann S., Fackler O.T., Großhans J., Grosse R. (2007) Positive feedback between Dia1, LARG and RhoA regulates cell morphology and invasion.
Brandt D.T., Marion S., Griffiths G., Watanabe T., Kaibuchi K., Grosse R. (2007) Dia1 and IQGAP1 interact in cell migration and phagocytic cup formation.
