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Multiple interactions recruit BLTP2 to ER-PM contacts to control plasma membrane dynamics
Anbang Dai1,2,3,4, Peng Xu1,2,3,4, Chase Amos1,2,3,4
1Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA.
The Journal of Cell Biology
|September 3, 2025
Summary
Bridge-like lipid transfer protein 2 (BLTP2) facilitates bulk lipid transport between the ER and plasma membrane (PM). Its absence causes intracellular vacuole accumulation, highlighting BLTP2
Area of Science:
- Cell Biology
- Membrane Trafficking
- Lipid Metabolism
Background:
- Bridge-like lipid transfer protein 2 (BLTP2/KIAA0100) localizes to ER contact sites with the plasma membrane (PM) or recycling tubular endosomes.
- The precise function of BLTP2 in lipid transport and membrane dynamics remains incompletely understood.
Purpose of the Study:
- To elucidate the role of BLTP2 in mediating lipid transport between the endoplasmic reticulum (ER) and the plasma membrane (PM).
- To identify the molecular interactions enabling BLTP2 binding to the PM and its function in membrane dynamics.
Main Methods:
- Cell-based assays to observe BLTP2 localization and function.
- Identification of protein and lipid interaction partners of BLTP2 at the PM.
- Analysis of cellular phenotypes in BLTP2-deficient cells.
Main Results:
- BLTP2 tethers the ER to tubular endosomes upon their continuity with the PM and to fusing macropinosomes.
- BLTP2 interacts with phosphoinositides, FAM102A/B adaptor proteins, and N-BAR domain proteins at membrane tubules.
- BLTP2 absence leads to intracellular vacuole accumulation, many connected to the PM.
Conclusions:
- BLTP2 is crucial for bulk lipid transport from the ER to the PM.
- BLTP2 plays a significant role in regulating plasma membrane dynamics through lipid transport.
- Deficiency in BLTP2 impairs cellular homeostasis by disrupting membrane trafficking and integrity.
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