The GET receptor as an entry gate to the ER and its interplay with GET bodies

Signal-recognition particle (SRP)-dependent, co-translational 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. We have also recently uncovered an additional function for Get3 as a chaperone. In this project, we will explore the regulated interaction of Get3 with its ER-based receptor and its reversible localization to cytoplasmic foci termed “GET bodies”. Interestingly, we have discovered that, as well as various chaperones, GET bodies contain a number of RNA-binding proteins, including tRNA modification enzymes, RNA helicases and mRNA decay factors. We will analyse the dynamic assembly of GET bodies as well as their physiological relevance to GET-dependent targeting and gene expression.