C 3-Professur für Physiologie (Schwab)
Röntgenring 9, 97070 Würzburg
Other participating persons and organisations:
Research foci (and basic equipment-based research projects):
Cell migration plays an important role in imany physiological and
pathophysiological processes. Examples include embryogenesis, immune
defense, wound healing and the formation of tumor metastases. A
characteristic property of migrating cells is their polarization within
the plane of movement. Front and rear parts of migrating cells can be
clearly distinguished from each other. Accordingly, the cytoskeleton, one
of the main motors of cell migration, is restructured differently in the
front and rear parts of crawling cells. We could show that, in addition to
cytoskeletal remodeling, the activity of a number of ion channels and
transporters is required for migration, too. A calcium-sensitive potassium
channel (IK1 channel) and the sodium-proton-exchanger (NHE1) are of
particular importance in this context. They influence the cytoskeletal
migration machinery by modulating cell volume. The effects of potassium
(IK1) channel activity are limited predominantly to the rear part of
migrating cells, while that of the sodium-proton-exchanger (NHE1) is
restricted to the cell front. We wanted to find out whether the polarized
distribution of potassium channel activity is due to an uneven
distribution of the channel protein or whether it is due to its
differential regulation at the opposing cell poles. Therefore, we cloned
the calcium-sensitive potassium channel from migrating cells and began to
study the molecular mechanisms of its regulation. Moreover, we also
investigated the functional role of potassium channels for migration of
human neutrophil granulocytes.
Schwab, A., Reinhardt, J., Schneider, S. W., Gaßner, B., Schuricht, B.
1999. K+ channel dependent migration of fibroblasts and human melanoma
cells. Cell. Physiol. Biochem. 9: 126-132
Schwab, A., Reinhardt, J., Seeger, P., Schuricht. B., Dartsch, P. C. 1999.
Migration of transformed renal epithelial cells is regulated by K+ channel
modulation of actin cytoskeleton and cell volume. Pflügers Arch. 438:
Warth, R., Hamm, K., Bleich, M., Kunzelmann, K., von Hahn, T., Schreiber,
R., Ullrich, E., Mengel, M., Trautmann, N., Kindle, P., Schwab, A., Greger,
R. 1999. Molecular and functional characterization of the small Ca2+
activated K+ channel (rSK4) of colonic crypts. Pflügers Arch. 438: 437-444
Schneider, S. W., Danker, T., Reinhardt, J., Oberleithner, H., Schwab, A.
2000. Volume dynamics in migrating epithelial cells measured with atomic
force microscopy. Pflügers Arch. 439: 297-303
Klein, M., Seeger, P., Schuricht, B., Alper, S. L., Schwab, A. 2000.
Polarization of Na+/H+ and Cl-/HCO3- exchangers in migrating renal
epithelial cells. J. Gen. Physiol. 115: 599-607
Schwab, A. 2001. Ion channels and transporters on the move. News Physiol.
Sci. 16: 29-31
Schwab, A. 2001. Function and spatial distribution of ion channels and
transporters in cell migration. Am. J. Physiol. Renal Physiol. 280: