Dai Anbang, Xu Peng, Amos Chase, Fujise Kenshiro, Wu Yumei, Yang Han, Eisen Julia N, Guillén-Samander Andrés, De Camilli Pietro
Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA.
Department of Cell Biology, Yale University School of Medicine, New Haven, CT, USA.
J Cell Biol. 2025 Sep 3;224(11). doi: 10.1083/jcb.202504027.
BLTP2/KIAA0100, a bridge-like lipid transfer protein, was reported to localize at contacts of the ER with either the plasma membrane (PM) or recycling tubular endosomes depending on the cell type. Our findings suggest that mediating bulk lipid transport between the ER and the PM is a key function of this protein, as BLTP2 tethers the ER to tubular endosomes only after they become continuous with the PM and that it also tethers the ER to macropinosomes in the process of fusing with the PM. We further identify interactions underlying binding of BLTP2 to the PM, including phosphoinositides, the adaptor proteins FAM102A/FAM102B, and N-BAR domain proteins at membrane-connected tubules. The absence of BLTP2 results in the accumulation of intracellular vacuoles, many of which are connected to the PM, pointing to a role of the lipid transport function of BLTP2 in the control of PM dynamics.
BLTP2/KIAA0100是一种桥状脂质转运蛋白，据报道，根据细胞类型的不同，它定位于内质网与质膜（PM）或循环管状内体的接触部位。我们的研究结果表明，介导内质网与质膜之间的大量脂质运输是该蛋白的关键功能，因为BLTP2仅在管状内体与质膜连续后才将内质网与它们相连，并且在与质膜融合的过程中，它还将内质网与巨吞饮小体相连。我们进一步确定了BLTP2与质膜结合的潜在相互作用，包括磷酸肌醇、衔接蛋白FAM102A/FAM102B以及膜连接小管处的N-BAR结构域蛋白。BLTP2的缺失导致细胞内液泡的积累，其中许多与质膜相连，这表明BLTP2的脂质运输功能在控制质膜动态中发挥作用。
