Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Nat Cell Biol. 2012 Apr 8;14(5):488-501. doi: 10.1038/ncb2473.
Clathrin-mediated endocytosis occurs at multiple independent import sites on the plasma membrane, but how these positions are selected and how different cargo is simultaneously recognized is obscure. FCHO1 and FCHO2 are early-arriving proteins at surface clathrin assemblies and are speculated to act as compulsory coat nucleators, preceding the core clathrin adaptor AP-2. Here, we show that the μ-homology domain of FCHO1/2 represents an endocytic interaction hub. Translational silencing of fcho1 in zebrafish embryos causes strong dorsoventral patterning defects analogous to Bmp signal failure. The Fcho1 μ-homology domain interacts with the Bmp receptor Alk8, uncovering an endocytic component that positively modulates Bmp signal transmission. Still, the fcho1 morphant phenotype is distinct from severe embryonic defects apparent when AP-2 is depleted. Our data thus challenge the primacy of FCHO1/2 in coat initiation.
网格蛋白介导的内吞作用发生在质膜上多个独立的入口位点，但这些位置是如何被选择的，以及如何同时识别不同的货物，目前还不清楚。FCHO1 和 FCHO2 是质膜表面网格蛋白组装体上的早期到达蛋白，推测它们作为必需的衣被核启动子，先于核心网格蛋白衔接蛋白 AP-2。在这里，我们表明 FCHO1/2 的 μ 同源结构域代表了一个内吞相互作用枢纽。斑马鱼胚胎中 fcho1 的翻译沉默导致强烈的背腹模式缺陷，类似于 Bmp 信号失败。Fcho1 μ 同源结构域与 Bmp 受体 Alk8 相互作用，揭示了一个正向调节 Bmp 信号转导的内吞成分。然而，fcho1 形态发生缺陷与当 AP-2 耗尽时明显的严重胚胎缺陷不同。因此，我们的数据挑战了 FCHO1/2 在衣被起始中的首要地位。
