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Induced nanoscale membrane curvature bypasses the essential endocytic function of clathrin
Journal of Cell Biology ( IF 7.4 ) Pub Date : 2023-05-09 , DOI: 10.1083/jcb.202109013
Robert C Cail 1 , Cyna R Shirazinejad 1 , David G Drubin 1, 2
Affiliation  

During clathrin-mediated endocytosis (CME), flat plasma membrane is remodeled to produce nanometer-scale vesicles. The mechanisms underlying this remodeling are not completely understood. The ability of clathrin to bind membranes of distinct geometries casts uncertainty on its specific role in curvature generation/stabilization. Here, we used nanopatterning to produce substrates for live-cell imaging, with U-shaped features that bend the ventral plasma membrane of a cell into shapes resembling energetically unfavorable CME intermediates. This induced membrane curvature recruits CME proteins, promoting endocytosis. Upon AP2, FCHo1/2, or clathrin knockdown, CME on flat substrates is severely diminished. However, induced membrane curvature recruits CME proteins in the absence of FCHo1/2 or clathrin and rescues CME dynamics/cargo uptake after clathrin (but not AP2 or FCHo1/2) knockdown. Induced membrane curvature enhances CME protein recruitment upon branched actin assembly inhibition under elevated membrane tension. These data establish that membrane curvature assists in CME nucleation and that the essential function of clathrin during CME is to facilitate curvature evolution, rather than scaffold protein recruitment.

中文翻译:

诱导的纳米级膜曲率绕过了网格蛋白的基本内吞功能

在网格蛋白介导的内吞作用(CME)过程中,平坦的质膜被重塑以产生纳米级的囊泡。这种重塑的机制尚不完全清楚。网格蛋白结合不同几何形状的膜的能力使其在曲率生成/稳定中的具体作用产生不确定性。在这里,我们使用纳米图案来生产用于活细胞成像的基底,其具有 U 形特征,可以将细胞的腹侧质膜弯曲成类似于能量上不利的 CME 中间体的形状。这种诱导的膜曲率会招募 CME 蛋白,促进内吞作用。AP2、FCHo1/2 或网格蛋白敲低后,平面基底上的 CME 会严重减弱。然而,诱导膜曲率在缺乏 FCHo1/2 或网格蛋白的情况下招募 CME 蛋白,并在网格蛋白(但不是 AP2 或 FCHo1/2)敲低后挽救 CME 动力学/货物摄取。在升高的膜张力下,诱导的膜曲率增强了分支肌动蛋白组装抑制时的 CME 蛋白募集。这些数据证实膜曲率有助于 CME 成核,并且网格蛋白在 CME 过程中的基本功能是促进曲率进化,而不是招募支架蛋白。
更新日期:2023-05-09
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