Growth factor control of integrin dependent cell migration of cells of the melanocyte lineage
Research theme of the group:
What mechanisms are responsible for the formation of metastasis? How is cell migration through a complex 3D environment controlled? What are the signals in the tissue that influence migrating cells? How are these signals presented to the migrating cells? What are the mechanisms that control the reversible anchorage to the extracellular matrix in migrating cells? How are receptors for the extracellular matrix anchored in the cell surface and how is the architecture and mechanical properties of the extracellular matrix transformed into biochemical information controlling cell migration?
To answer these and similar questions is the goal of our research group here in the Centre Médical Universitaire. Since several years, we have been using cell biological techniques to understand the cell surface presentation of the transmembrane growth factor Kit-ligand and the migratory response of melanocytes towards this growth factor. Melanocytes express c-kit, the receptor for Kit-ligand on their surface and migrate chemotactically towards this growth factor. During this migration, melanocytes reversibly engage heterodimeric cell surface receptors of the integrin family. Integrin activation and subsequent clustering into cell-substrate adhesion sites is a tightly controlled process, which is of critical importance for embryogenesis, immunity, wound healing and the formation of metastasis.
With the help of live-cell imaging techniques based on the green fluorescent protein, we are dissecting the dynamics and the molecular mechanisms of these processes in living cells. The goal of our research is to identify the critical steps that control cell migration, forming the therapeutic targets, which will eventually allow reverting pathological conditions that are linked to a deregulation of cell migration.
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Wehrle-Haller, B. and Imhof, B. A. (2002). The inner lives of focal adhesions. Trends in Cell Biology, 12, 382-389.
Wehrle-Haller, B. and Imhof, B. A. (2003). Actin, microtubules and focal adhesion dynamics during cell migration. International Journal of Biochemistry and Cell Biology, 35, 39-50.
Wehrle-Haller, B. (2003). The role of kit-ligand in melanocyte development and epidermal homeostasis. Pigment Cell Research, 16, 287-296.
Wehrle-Haller, B. and Imhof, B. A. (2003). Integrin-dependent pathologies. Journal of Pathology, 200, 481-487.
Lehnert, D., Wehrle-Haller, B., David, C., Ballestrem, C., Imhof, B. A. and Bastmeyer, M. (2004). Cell behavior on micropatterned substrates: limits of extracellular matrix geometry for spreading and adhesion. Journal of Cell Science 117, 41-52.
Paulhe, F., Imhof, B.A. and Wehrle-Haller, B. (2004). A specific ER-export signal drives transport of Stem cell factor (Kitl) to the cell surface. Journal of Biological Chemistry 279, 55545-55.
Cluzel, C., Saltel, F. Lussi, J. Paulhe, F., Imhof, B.A. and Wehrle-Haller, B. (2005). The mechanisms of integrin clustering in living cells. Journal of Cell Biology 171, 383-392.
Wehrle-Haller, B. (2005). The role of integrins in cell migration. In Integrins in Development Edited by E. Danen, Landes Bioscience, Georgetown, TX USA.
“Stem cell factor: Basolateral sorting signal and inhibitors thereof”. Inventors: B. Wehrle-Haller and B. A. Imhof. PCT/EP00/13141.