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

Neuman, Sarah1; Cavanagh, Amy1; Sheffels, Nicole1; Conibear, Elizabeth2; Bashirullah, Arash13

Published Apr 22, 2026 on Dryad. https://doi.org/10.5061/dryad.9w0vt4bwm

Data files

Apr 22, 2026 version files 165.96 KB

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Abstract

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 Drosophila as a model system to dissect the mechanisms that drive targeting of BLTP2 (hobbit in Drosophila) to endoplasmic reticulum-plasma membrane (ER-PM) contact sites. We demonstrate that a conserved adapter protein, which we name bilbobaggins (bbo), is required for targeting of Hobbit to ER-PM contacts; importantly, loss of bbo phenocopies loss of hobbit, indicating that bbo is required for hobbit function. Additionally, our structure-function analyses show that cis-acting sequences in the C-terminal tail of Hobbit are also required for ER-PM targeting. Crucially, our data indicate that these cis-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.