Bridge-like lipid transfer protein family member 2 suppresses ciliogenesis
Jan Parolek1, Christopher G Burd1
1Department of Cell Biology, Yale School of Medicine, New Haven, CT 06520.
Abstract:
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 β-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 in RPE-1 cells grown in serum-containing medium, a condition where ciliogenesis is normally suppressed. This study establishes human BLTP2 as a putative LTP acting between tubular endosomes and ER that regulates primary cilium biogenesis.
Insights
Bridge-like lipid transfer protein family member 2 (BLTP2) regulates primary cilium formation. BLTP2 acts as a lipid transfer protein between the endoplasmic reticulum and endosomes, impacting ciliogenesis.
Area of Science:
- Cell Biology
- Molecular Biology
- Protein Function
Background:
- Bridge-like lipid transfer protein family member 2 (BLTP2) is conserved across species but its function remains largely unknown.
- BLTP2 absence leads to severe developmental defects, including larval death in fruit flies and preweaning lethality in mice.
- Structural predictions suggest BLTP2 functions as a lipid transfer protein (LTP) within the VPS13 family.
Purpose of the Study:
- To elucidate the function of BLTP2 in cellular processes.
- To investigate the role of BLTP2 in ciliogenesis.
- To determine the subcellular localization and potential lipid transfer activity of BLTP2.
Main Methods:
- Genetic interaction studies with WDR44 in RPE-1 cells.
- Subcellular localization analysis in HeLa cells using microscopy.
- Assessment of ciliogenesis in RPE-1 cells under different culture conditions.
Main Results:
- BLTP2 was identified as a negative regulator of ciliogenesis, with its depletion enhancing primary cilium formation.
- BLTP2 localizes to membrane contact sites between the endoplasmic reticulum and tubular endosomes.
- BLTP2 depletion promoted ciliogenesis in serum-containing medium, where it is typically suppressed.
Conclusions:
- Human BLTP2 is proposed to be a lipid transfer protein functioning between the endoplasmic reticulum and tubular endosomes.
- BLTP2 plays a regulatory role in the biogenesis of primary cilia.
- The study provides new insights into the function of BLTP2 and its involvement in cellular secretion and development.
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