Abstract 2046 Regulating targeting of bulk lipid transport proteins to membrane contact sites

Bridge-like lipid transfer proteins (BLTPs) are a novel family of lipid transporters that engage in bulk movement of lipids at organelle membrane contact sites. Mutations in several of the BLTPs are associated with human disease. Although recent work has begun to uncover mechanisms by which BLTPs move lipids, much remains unknown about how BLTP-dependent lipid transfer function is regulated. Our work has identified subcellular targeting as a critical mechanism that regulates BLTP function. Using a combination of in silico, in vitro, and in vivo approaches, we found that targeting of BLTP2 to endoplasmic reticulum-plasma membrane (ER-PM) contact sites is controlled by binding to a specific adapter protein and by binding to specific lipid moieties. Moreover, we found that BLTP2 enrichment at ER-PM contacts is dynamically controlled during development. Together, these findings highlight new layers of regulation that govern lipid transfer at membrane contact sites.