| Biogenesis of plasma membrane proteins
Most secreted and membrane proteins contain hydrophobic signal sequences that target their synthesis to the endoplasmic reticulum (ER). Beside that, certain mRNAs are transported within the cell, suggesting a local protein synthesis at specific domains of the ER. Over the past five years, we have worked on the biogenesis of the polytopic membrane protein Ist2 in yeast, which mRNA is localized to the periphery of daughter cells. We found that the trafficking of Ist2 from the ER to the plasma membrane occurs independently of the function of the secretory (Sec)-pathway. Our current research has shown, that the transport of proteins on this route requires an insertion of the synthesized protein into the ER membrane and a unique protein-sorting signal.
We use the model system Saccharomyces cerevisiae, in order to address the following questions:
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The identification of lipids and/or proteins that are responsible for Sec-independent transport from the ER to the plasma membrane. We propose that such factors mediate a concentration of Ist2 protein at specific ER sites, from where the Ist2 protein reaches – by a yet unknown mechanism - the plasma membrane. To find these factors, we perform a variety of genetic screens.
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As a complementary approach, we search biochemically for components that interact with the sorting signal of Ist2. Furthermore, we will characterize features of the Ist2 sorting signal in greater detail in order to define a consensus sequence for this sorting signal.
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In addition to that we are starting experiments in mammalian systems and try to find out whether other proteins use this novel pathway to the cell surface, too.
Selected Publications
Frey, S., Pool, M. and Seedorf, M. (2001). Scp160p, an RNA-binding, polysome-associated protein localizes to the endoplasmic reticulum of Saccharomyces cerevisiae in a microtubule-dependent manner. J. Biol. Chem. 276:15905-15912.
Jüschke, C., Ferring, D., Jansen, R.-P. and Seedorf, M. (2004). A novel transport pathway for a yeast plasma membrane protein encoded by a localized mRNA. Current Biology 14:406-411.
Baum, S., Bittins, M., Frey, S. and Seedorf, M. (2004). Asc1, a WD40-domain containing adaptor protein, is required for the interaction of the RNA-binding protein Scp160p with polysomes. Biochem. J. 380:823-830.
Jüschke, C., Wächter, A., Schwappach, B. and Seedorf, M. (2005). SEC18/NSF-independent, protein-sorting pathway from the yeast cortical ER to the plasma membrane. J. Cell Biol. 169:613-622.
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