Profilin II : novel functions in membrane trafficking
Profilin II - Novel functions in membrane-trafficking Ralph Gareus - EMBL Mouse Biology Programme, Monterotondo, Italy Profilin is an actin-binding protein expressed in all eukaryotic cells, regulating microfilament remodelling. Besides actin, it binds to poly-L-proline and phosphatidylinositol phoshates. Mice have three profilin genes, with profilin I being ubiquitously expressed, profilin II a brain specific isoform and profilin III expressed in kidney and testis. Via its poly-L-proline binding site profilin I and profilin II bind to ligands which had been shown to not only regulate the microfilament system, but also signal transduction and membrane traffic, suggesting novel, not yet investigated functions for the profilins. One goal of this thesis was to analyze protein ligands for profilin I and profilin II in different mouse tissues, thus getting further insight on potential profilin functions. Novel binding partners found for profilin I were the glycolytic enzyme GAPDH and the putative G-protein coupled receptor p40, further suggesting the idea of an involvement of profilin in signal transduction processes. The huntingtin-protein, mutations of which give rise to Huntington's disease and the phosphatidylinositol phosphatase synaptojanin were identified as new profilin II ligands, which are not found in the profilin I complex, linking this profilin isoform to lipid metabolism and disease. The second goal of this thesis was to address the question of a possible role for profilin II in membrane trafficking, as suggested by a number of protein ligands found in the affinity complexes from mouse brain. As shown in this work, profilin II acts as a negative regulator of membrane uptake. Overexpression of profilin II in cells inhibits membrane uptake and vice versa neurons from mice lacking this profilin isoform show an increase in membrane recycling. The effects are most likely mediated by direct interaction of profilin II with ligands such as POP-130, wh
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