Banerjee Subhrajit, Daetwyler Stephan, Bai Xiaofei, Michaud Morgane, Jouhet Juliette, Binns Derk, Madhugiri Shruthi, Johnson Emma, Wang Chao-Wen, Fiolka Reto, Toulmay Alexandre, Prinz William A
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nat Cell Biol. 2025 Jun 27. doi: 10.1038/s41556-025-01672-3.
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.
脂质转运蛋白（LTPs）促进细胞区室之间的非囊泡脂质交换，并在脂质稳态中发挥关键作用。最近发现的一类桥状LTPs（BLTPs）被认为在细胞器之间形成脂质运输通道。其中之一，BLTP2，在物种间保守，但其功能尚不清楚。在这里，我们表明BLTP2通过增加质膜（PM）中的磷脂酰乙醇胺（PE）水平来调节质膜流动性。BLTP2定位于内质网（ER）-质膜接触位点，并在体内运输PE，表明它驱动PE从内质网向质膜移动。我们发现BLTP2与另一条调节细胞内PE分布和质膜流动性的途径并行发挥作用。BLTP2的表达与乳腺癌的侵袭性相关。我们发现BLTP2促进三阴性乳腺癌细胞系的生长，并在转移的体内模型中维持其侵袭性，这表明BLTP2维持质膜流动性可能对人类肿瘤发生至关重要。
