Receptor-mediated endocytosis of soluble and membrane-tethered Sonic hedgehog by Patched-1
Receptor-mediated endocytosis of soluble and membrane-tethered Sonic hedgehog by Patched-1
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DOI：
10.1073/pnas.220251997
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发表时间：
2000-10-24
影响因子：
11.1
通讯作者：
Roelink, H
中科院分区：
文献类型：
--
作者：
Incardona, JP;Lee, JH;Roelink, H
patch （Ptc）是Hedgehog （Hh）受体复合物的配体结合成分。在果蝇胚胎中，Ptc和Hh在囊状点状结构中共定位。然而，受体介导的Hh蛋白内吞作用尚未得到证实。通过使用鸡神经板外植体，我们发现Sonic hedgehog （Shh）应答的神经前体细胞内化了重组Shh和内源性Shh，并为腹侧神经管内源性Shh的梯度提供了直接证据。Shh内化被单克隆抗体阻断，其表位与Shh的ptc结合位点重叠。这些发现表明Shh内化是由ptc - 1介导的，并且可能与信号传导有关。同样，Ptc-l cDNA转染哺乳动物细胞系，可以通过动力蛋白依赖过程内化多种形式的Shh，包括跨膜锚定Shh。
Patched (Ptc) is the ligand-binding component of the Hedgehog (Hh) receptor complex. In the Drosophila embryo, Ptc and Hh colocalize in vesicular punctate structures. However, receptor-mediated endocytosis of Hh proteins has not been demonstrated. By using chick neural plate explants, we show that Sonic hedgehog (Shh)-responsive neural precursor cells internalize recombinant and endogenous Shh and provide direct evidence for a gradient of endogenous Shh in the ventral neural tube. Shh internalization is blocked by a monoclonal antibody whose epitope overlaps the Ptc-binding site of Shh. These findings suggest that Shh internalization is mediated by Ptc-l and may be linked to signaling. Concordantly, transfection of mammalian cell lines with a Ptc-l cDNA confers the ability to internalize multiple forms of Shh, including transmembrane-anchored Shh, by a dynamin-dependent process.