The GET receptor as an entry gate to the ER
Signal-recognition particle (SRP)-dependent, cotranslational targeting to the endoplasmic reticulum (ER) membrane is a well-characterized process but many SRP-independent precursor proteins exist. We have co-discovered the 'guided entry of tail-anchored (TA) proteins' (GET) pathway, an SRP-independent targeting system that ensures the posttranslational integration of TA membrane proteins of the secretory pathway without involvement of the translocon. In addition, a translocon-dependent role for the GET pathway in the ER targeting of small secretory and GPI-anchored proteins is emerging. Here, we will delineate the full physiological cargo spectrum of the GET pathway and its overlap with that of other targeting pathways. We will address how the GET receptor complex at the ER membrane is harnessed to support the targeting of substrates with different requirements, e.g. membrane integration versus translocation. We will dissect the protein-protein interactions of the yeast and mammalian GET receptor complex with different types of substrates and with machinery involved in protein translocation. The project will provide new insight into how this membrane protein complex provides a versatile gate for the entry and subsequent processing of diverse precursors at the ER.
Prof. Dr. Blanche Schwappach
University Medical Center Göttingen
Department of Molecular Biology
+49 551 39 5962 (phone)