The Vps13-like protein BLTP2 regulates phosphatidylethanolamine levels to maintain plasma membrane fluidity and breast cancer aggressiveness
Lipid transport proteins (LTPs) facilitate non-vesicular lipid exchange between cellular compartments and have critical roles in lipid homeostasis. A recently identified family of bridge-like LTPs (BLTPs) is thought to form lipid-transporting conduits between organelles. One of these, BLTP2, is conserved across species but its function is not known. Here we show that BLTP2 regulates plasma membrane (PM) fluidity by increasing phosphatidylethanolamine (PE) levels in the PM. BLTP2 localizes to endoplasmic reticulum (ER)-PM contact sites, and transports PE in vivo, suggesting it drives PE movement from ER to PM. We find that BLTP2 works in parallel with another pathway that regulates intracellular PE distribution and PM fluidity. BLTP2 expression correlates with breast cancer aggressiveness. We found that BLTP2 facilitates growth of a triple negative breast cancer cell line and sustains its aggressiveness in an in vivo model of metastasis, suggesting maintenance of PM fluidity by BLTP2 may be critical for tumorigenesis in humans.
Authors
- Reto Fiolka (ORCID: https://orcid.org/0000-0002-4636-5000)
- Xiaofei Bai (ORCID: https://orcid.org/0000-0001-8179-8162)
- Alexandre Toulmay (ORCID: https://orcid.org/0009-0009-5383-3632)
- Juliette Jouhet (ORCID: https://orcid.org/0000-0002-4402-2194)
- William A. Prinz (ORCID: https://orcid.org/0000-0002-9053-2398)
- Subhrajit Banerjee (ORCID: https://orcid.org/0000-0003-1474-8864)
- Stephan Daetwyler (ORCID: https://orcid.org/0000-0002-7444-4734)
- Derk D. Binns (ORCID: https://orcid.org/0000-0003-4949-3507)
- Chao-Wen Wang (ORCID: https://orcid.org/0000-0002-4073-299X)
- Morgane Michaud (ORCID: https://orcid.org/0000-0002-4853-8411)
- Shruthi Madhugiri
- Emma Johnson
Institutions
- Centre National de la Recherche Scientifique (FR)
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- CEA Grenoble (FR)
- University of Florida (US)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Southwestern Medical Center (US)
- The University of Texas Southwestern Medical Center (US)
- Université Grenoble Alpes (FR)
- National Cheng Kung University (TW)
Publication Details
- Journal
- Nature Cell Biology
- Published
- 2025-06-27
- DOI
- https://doi.org/10.1038/s41556-025-01672-3
- Citations
- 10
- Primary Topic
- Lipid Membrane Structure and Behavior
- Type
- article
- Field-Weighted Citation Impact
- 8.06
Funders
- Center for Strategic Scientific Initiatives, National Cancer Institute
- Agence Nationale de la Recherche
- National Cancer Institute
- National Institute of General Medical Sciences
- National Institute of Diabetes and Digestive and Kidney Diseases