Bridge-like lipid transfer protein family member 2 suppresses ciliogenesis
Bridge-like lipid transfer protein family member 2 (BLTP2) is an evolutionary conserved protein with unknown function(s). The absence of BLTP2 in Drosophila melanogaster results in impaired cellular secretion and larval death, while in mice (Mus musculus), it causes preweaning lethality. Structural predictions propose that BLTP2 belongs to the repeating {beta}-groove domain-containing (also called the VPS13) protein family, forming a long tube with a hydrophobic core, suggesting that it operates as a lipid transfer protein (LTP). We establish BLTP2 as a negative regulator of ciliogenesis in RPE-1 cells based on a strong genetic interaction with WDR44, a gene that also suppresses ciliogenesis. Like WDR44, BLTP2 localizes to membrane contact sites involving the endoplasmic reticulum and the tubular endosome network in HeLa cells and that BLTP2 depletion enhanced ciliogenesis by serum-fed RPE-1 cells, a condition where ciliogenesis is normally suppressed. This study establishes human BLTP2 as a putative lipid transfer protein acting between tubular endosomes and ER that regulates primary cilium biogenesis. Significance statementWe show the involvement of an ER-localized bridge-like lipid transfer protein, BLTP2, in ciliogenesis and establish that BLTP2 is enriched at organelle-organelle membrane contact sites involving the endoplasmic reticulum (ER) and the tubular endosome network (TEN). These results implicate, for the first time, the involvement of bulk lipid transfer between the ER and TEN in regulating ciliogenesis.