The Department of Biomedicine

BBB seminar: Anna Starzinski-Powitz

Role of adherens junctional protein shrew-1 in cellular invasiveness

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Anna Starzinski-Powitz
Institute of Anthropology and Human Genetics for Biologists, Johann Wolfgang Goethe University, Frankfurt/Main, Germany

We recently isolated the novel membrane protein shrew-1, which appeared to be associated with an invasive cellular background. Over the past years, we could present evidence that shrew-1 has obviously different roles in cells. On the one hand, shrew-1 targets to mature adherens junctions (AJ), a dynamic network of E-cadherin-mediated membrane proteins in polarized (i.e. non-invasive) epithelial cells where it performs a so far unknown function. Shrew-1’s targeting to AJs is controlled by its cytoplasmic domain, in detail by tyrosine- and leucine-based sorting motifs located there. In contrast to this, shrew-1 influences invasion of non-polarised cells into extra cellular matrix (ECM). Inhibition of shrew-1 by siRNA reduces cell invasion, while its overexpression leads to increased invasion of cells into ECM. Consistent with this is the finding that shrew-1 is able to interact with invasion-controlling, MMP-inducing membrane protein CD147/EMMPRIN, which is also a regulatory subunit of gamma-secretase. So far, our results raise the possibility that shrew-1 is involved in the dynamics between the migratory and non-migratory phenotype of cells and thus might influence metastasis mechanisms.

Host: Donald.Gullberg, Department of Biomedicine

Anna Starzinski-Powitz

Anna Starzinski-Powitz did her PhD work on the immunogenetics of T-cells at the University of Mainz, Germany, followed by a postdoc at the Pasteur Institute in Paris under the direction of Nobel laureate Francis Jacob, working on the immunological characterization of teratomas and teratocarcinomas. After a second postdoc period in Walter Doerfler's lab at the Institute of Genetics in Cologne, Germany, she became group leader at this institute, working on different aspects of muscle development. In 1991 she was appointed to a full professorship in Human Genetics at the Johann Wolfgang Goethe University in Frankfurt/Main, Germany. Anna Starzinski-Powitz’s research interests include: cadherin-mediated intercellular communications, cadherins in morphogenesis and membrane-mediated signal transduction, structure-function relationship of the transmembrane protein shrew-1 and its role in invasion and metastasis, structure and function of catenins, pathogenesis of endometriosis.

Anna Starzinski-Powitz is founding member and Managing Director of the “Centre for Membrane Proteomics” (CMP) at the Goethe University, as well as initiator of the CMP’s pilot mentoring programme “SciMento” for young female scientists.

Selected publications:
1) Bharti, S., Handrow-Metzmacher, H., Zickenheiner, S., Zeitvogel, A., Herrmann, G., Baumann, R. and Starzinski-Powitz, A. (2004) Novel membrane protein shrew-1 targets to cadherin-mediated junctions in polarised epithelial cells. Mol. Biol. Cell, 15, 397-406.
2) McDonald. J.M., Dunlap, S., Cogdell. D., Dunmire, V., Wei, Q., Starzinski-Powitz, A., Sawaya, R., Bruner, J., Fuller, G.N., Aldape, K., and Zhang, W. (2006) The SHREW1 gene, frequently deleted in oligodendrogliomas, functions to inhibit cell adhesion and migration. Cancer Biol. Ther., 5, 300-4.
3) Jakob, V., Schreiner, A., Tikkanen, R. and Starzinski-Powitz, A. (2006) Targeting of transmembrane protein shrew-1 to adherens junctions is controlled by cytoplasmic sorting motifs. Mol. Biol. Cell. In press.

Homepage: http://www.bio.uni-frankfurt.de/humagen/02_gebiet/gebiet_0.htm