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

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.