Abstracts
Building a functional atlas of homologous contact site machineries through advanced interaction mapping
Presenting author: Emma Fenech
University of Cologne, Center for Biochemistry, Joseph-Stelzmann-Straße 52, 50931 Cologne [DE], efenech@uni-koeln.de
Author(s):
Emma Fenech
The endoplasmic reticulum (ER) coordinates a multitude of diverse and essential functions. The range and robustness of each of these functions are upheld by the unique and shared capacities of homologous proteins. Such homologs are also present at ER contact sites, with the yeast family of six LAM (Lipid transfer protein Anchored at Membrane contact sites) proteins being one example. This family is composed of three pairs of homologs which are all anchored in the ER membrane and contain lipid binding and transfer domains. However, each LAM protein is unique in its molecular architecture and localization to different ER subdomains. To shed light onto what determines the localization of the different LAMs and the specific roles they perform, we used an advanced proximity-labelling approach to profile the protein landscape of the entire family. We uncovered unique candidate interactors which supported previous observations that Lam5 resides at the ER-mitochondria contact, and we demonstrated a novel role for it in sustaining mitochondrial activity. Conversely, shared putative interactors of multiple LAMs revealed how the Lam1/3 and Lam2/4 homologous pairs could associate specifically with plasma membrane lipids. Overall, our work provides new insights into the regulation and function of the LAM family members. More globally, it demonstrates how proximity labelling can identify shared and unique functions of protein homologs resident within the ER membrane contact site network.