Banerjee Subhrajit, Daetwyler Stephan, Bai Xiaofei, Michaud Morgane, Jouhet Juliette, 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.
bioRxiv. 2024 Feb 5:2024.02.04.578804. doi: 10.1101/2024.02.04.578804.
Lipid transport proteins (LTPs) facilitate nonvesicular lipid exchange between cellular compartments and have critical roles in lipid homeostasis. A new family of bridge-like LTPs (BLTPs) is thought to form lipid-transporting conduits between organelles. One, BLTP2, is conserved across species but its function is not known. Here, we show that BLTP2 and its homolog directly regulate plasma membrane (PM) fluidity by increasing the phosphatidylethanolamine (PE) level in the PM. BLTP2 localizes to endoplasmic reticulum (ER)-PM contact sites, suggesting it transports PE from the ER to the PM. We find BLTP2 works in parallel with another pathway that regulates intracellular PE distribution and PM fluidity. BLTP2 expression correlates with breast cancer aggressiveness. We found BLTP2 facilitates growth of a human 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。一类新的桥状LTPs（BLTPs）被认为在细胞器之间形成脂质运输通道。其中一种，即BLTP2，在物种间保守，但其功能尚不清楚。在此，我们表明BLTP2及其同源物通过增加质膜（PM）中的磷脂酰乙醇胺（PE）水平来直接调节质膜流动性。BLTP2定位于内质网（ER）-质膜接触位点，表明它将PE从内质网转运至质膜。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的表达与乳腺癌侵袭性相关。我们发现BLTP2促进一种人类癌细胞系的生长，并在体内转移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。
