- Studium der Biologie, ETH Zürich
- Promotion zum Dr. rer.nat., ETH Zürich
- Postoctoral Fellow, The Rockefeller University, New York, USA
- Assistant Professor, The Rockefeller University, New York, USA
- Leiter einer selbständigen Nachwuchsgruppe, Friedrich Miescher Laboratorium in der Max-Planck Gesellschaft, Tübingen
- Habilitation, Eberhard-Karls-Universität Tübingen
- Oberassistent, Adolf-Butenandt Institut, LMU München
- Professor für Zoologie, Institut für Allgemeine Zoologie und Genetik, WWU Münster
Functions of myosin molecules (DFG: SFB 629; GRK1050; Ba 1354/6-1)
Myosins are a large family of structurally diverse molecular motors that convert chemical energy derived from ATP-hydrolysis into mechanical force along actin filaments. They are involved in many different cellular processes that are dependent on directed forces like changes in cell morphology, cell migration, cell adhesion, cytokinesis and organelle transport and dynamics. The myosins exhibit different motor properties that are optimally adapted to their respective cellular functions. Furthermore, they have aquired multiple additional functional domains that serve as cargo, cargo receptors or regulatory elements. We are trying to understand how selected myosins function as single molecules, in the cellular context and in the organism. The methodological approaches include a broad set of methods from cell biology, molecular biology, biochemistry, biophysics and mouse technology.
Dynamic organization and functions of the actin cytoskeleton (Funding DFG: SPP 1150)
A dynamic cytoskeleton allows cells to change their morphology and intracellular organization. These changes in cytoskeletal organization are highly coordinate and complex processes that play important roles in e.g. development, wound healing, immune defense, hearing and cancer. The actin cytoskeleton consists of functionally different subsets of actin filament arrays that coexist in cells. They are populating different or overlapping regions of the cell. Their dynamics and distribution within cells are controlled by a large set of actin-binding proteins. We are studying the functions of particular actin-binding proteins that control the dynamics and organization of actin filament arrays involved in cell migration and macropinocytosis. Macropinocytosis refers to the formation of large endocytic vesicles (macropinosomes), generated by actin-driven circular ruffles of the plasma membrane. Macropinocytosis has an important function in the adaptive immune response, as dendritic cells which present processed antigens to T-cells, take up antigens by macropinocytosis.
- 10.1002/jbmr.3192. . ‘The RhoGAP Myo9b Promotes Bone Growth by Mediating Osteoblastic Responsiveness to IGF-1.’ Journal of Bone and Mineral Research 32, Nr. 10: 2103-2115. doi:
- 10.1074/jbc.M116.766923. . ‘Multiple roles of filopodial dynamics in particle capture and phagocytosis and phenotypes of Cdc42 and Myo10 deletion.’ Journal of Biological Chemistry 292, Nr. 17: 7258-7273. doi:
- 10.3389/fnmol.2016.00001. . ‘Myosin IXa binds AMPAR and regulates synaptic structure, LTP, and cognitive function.’ Frontiers in Molecular Neuroscience 9, Nr. null. doi:
- 10.1038/srep25016. . ‘Real-time two- and three-dimensional imaging of monocyte motility and navigation on planar surfaces and in collagen matrices: Roles of Rho.’ Scientific Reports 6, Nr. null. doi:
- 10.1002/cm.21292. . ‘Mice lacking myosin IXb, an inflammatory bowel disease susceptibility gene, have impaired intestinal barrier function and superficial ulceration in the ileum.’ Cytoskeleton 73, Nr. 4: 163-179. doi:
- 10.1016/j.jneuroim.2015.03.014. . ‘The motorized RhoGAP myosin IXb (Myo9b) in leukocytes regulates experimental autoimmune encephalomyelitis induction and recovery.’ Journal of Neuroimmunology 282, Nr. null: 25-32. doi:
- 10.1152/ajprenal.00220.2014. . ‘Rho GAP myosin IXa is a regulator of kidney tubule function.’ American Journal of Physiology - Renal Physiology 309, Nr. 6: F501-F513. doi:
- . . ‘Mouse Macrophages completely lacking Rho subfamily GTPases (RhoA, RhoB, and RhoC) have severe lamellipodial retraction defects, but robust chemotactic navigation and altered motility.’ Journal of Biological Chemistry 289, Nr. 44: 30772-30784. doi: 10.1074/jbc.M114.563270.
- . . ‘The Loop2 Insertion of Type IX Myosin Acts as an Electrostatic Actin Tether that Permits Processive Movement.’ PLoS ONE 9, Nr. 1: e84874. doi: doi:10.1371/journal.pone.0084874.
- . . ‘Dendritic cell motility and T cell activation requires regulation of Rho-cofilin signaling by the RhoGAP myosin IXb.’ Journal of Immunology 192: 3559-3568.
- . ‘Transient P2X7 Receptor Activation Triggers Macrophage Death Independent of Toll-like Receptors 2 and 4, Caspase-1, and Pannexin-1 Proteins.’ Journal of Biological Chemistry 287, Nr. 13: 10650-10663.
- . . ‘Real-time imaging reveals that P2Y2 and P2Y12 receptor agonists are not chemoattractants and macrophage chemotaxis to complement C5a is phosphatidylinositol 3-kinase (PI3K)- and p38 mitogen-activated protein kinase (MAPK)-independent.’ The Journal of biological chemistry 286, Nr. 52: 44776-87. doi: 10.1074/jbc.M111.289793.
- . . ‘Cellular functions of class IX myosins in epithelia and immune cells.’ Biochem Soc Trans 39, Nr. 5: 1166-8.
- . . ‘Paracellular permeability of bronchial epithelium is controlled by CFTR.’ Cell Physiol Biochem 28, Nr. 2: 289-96.
- . . ‘Head of myosin IX binds calmodulin and moves processively toward the plus-end of actin filaments.’ The Journal of biological chemistry 285, Nr. 32: 24933-42. doi: 10.1074/jbc.M110.101105.
- . . ‘Motorized RhoGAP myosin IXb (Myo9b) controls cell shape and motility.’ Proc Natl Acad Sci U S A 107, Nr. 27: 12145-50. doi: 10.1073/pnas.0911986107.
- . . ‘Myosin 1G (Myo1G) is a haematopoietic specific myosin that localises to the plasma membrane and regulates cell elasticity.’ FEBS Lett 584, Nr. 3: 493-9.
- . . ‘Myosin IXa regulates epithelial differentiation and its deficiency results in hydrocephalus.’ MBoC 20, Nr. 24: 5074-85. doi: 10.1091/mbc.E09-04-0291.
- . . ‘The Myosin IXb motor activity targets the myosin IXb RhoGAP domain as cargo to sites of actin polymerization.’ Molecular biology of the cell 18, Nr. 4: 1507-18. doi: 10.1091/mbc.E06-08-0771.
- . . ‘SWAP-70 associates transiently with macropinosomes.’ European journal of cell biology 86, Nr. 1: 13-24. doi: 10.1016/j.ejcb.2006.08.005.