Function of cortical domains of the endoplasmic reticulum

• Applicant: Privatdozent Dr. Matthias Seedorf
• Subject Area: Cell Biology
• Term: from 2005 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 20250808

Eukaryotic cells use the secretory (SEC)-pathway for the biogenesis of plasma membrane proteins. Our recent studies with the model organism Saccharomyces cerevisiae have shown that an alternative pathway exists for the trafficking of an integral membrane protein to the plasma membrane. The protein Ist2p is transported from the endoplasmic reticulum (ER) to the cell surface independently of the function of the classical SEC-pathway. We have identified the cytosolic C-terminal domain of Ist2p (Ist2c) as a dominant targeting signal for the plasma membrane. When this domain is positioned at the C-terminus of other membrane proteins, it redirects the resulting chimeras to the plasma membrane. Since this mechanism operates dominantly over the targeting of proteins to other membranes, we postulate that the biogenesis of Ist2p is initiated by a local synthesis at specific domains of the ER. Most likely these domains are positioned at the cell periphery from where the protein travels by an unknown mechanism to the plasma membrane. In order to find the factors that are required for the trafficking of Ist2p, we will purify Ist2c-interacting proteins and perform a genetic screen to identify the required genes for this novel pathway.

• DFG Programme: Research Grants