The role of VAP in ER-plasma membrane bridges. (360G-Wellcome-082119_Z_07_Z)

We will study how the major yeast homologue of VAP (Scs2) plays a critical role in bridging from the ER to the plasma membrane (PM). The most important goal of the project is to identify the PM receptor for Scs2, likely to be an important discovery, because it binds human VAP, indicating conservation throughout eukaryotes. Our current data shows that this receptor is a PM component concentrated at sites of polarised growth (such as bud-tips) by the polarisome, but the receptor is not a previousl y defined polarisome component. Using a simple candidate approach (testing all proteins annotated to localise to the bud-tip, and all suggested interactors of Scs2) we have not found the PM receptor. Here, we will carry out a series of experimental approaches of ever-increasing complexity to identify the PM receptor of Scs2. In addition, we will use mutants made in our lab, in which ER-PM contacts are critically defective, to study how lack of ER-PM contact affects specific cellular activities. Finally, if work identifying the PM receptor of Scs2 is successful and time allows, we will apply similar techniques to discovering the interactors of Ice2, another ER protein involved in ER-PM bridges.