Data from: Mechanistic dissection of BLTP2 targeting to ER-PM contact sites

<b>Abstract</b><br/><p>The bridge-like lipid transfer proteins (BLTPs) are a novel superfamily of rod-shaped lipid transporters that engage in bulk non-vesicular movement of lipids at organelle membrane contact sites. The molecular and cellular functions of these proteins are still emerging; however, it is clear that one key aspect that regulates BLTP function is targeting to the appropriate membrane contact site(s). Here, we use <em>Drosophila</em> as a model system to dissect the mechanisms that drive targeting of <em>BLTP2</em> (<em>hobbit</em> in <em>Drosophila</em>) to endoplasmic reticulum-plasma membrane (ER-PM) contact sites. We demonstrate that a conserved adapter protein, which we name <em>bilbobaggins</em> (<em>bbo</em>), is required for targeting of Hobbit to ER-PM contacts; importantly, loss of <em>bbo</em> phenocopies loss of <em>hobbit</em>, indicating that <em>bbo</em> is required for <em>hobbit</em> function. Additionally, our structure-function analyses show that <em>cis</em>-acting sequences in the C-terminal tail of Hobbit are also required for ER-PM targeting. Crucially, our data indicate that these <em>cis</em>-acting sequences and Bbo binding are independent and likely sequential mechanisms that we propose function like a “hook” and “latch” to govern Hobbit targeting. Thus, we define a new regulatory paradigm governing targeting of BLTPs to membrane contact sites.</p>