Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS 340, Memphis, TN 38105, USA.
Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS 340, Memphis, TN 38105, USA.
Trends Cell Biol. 2019 May;29(5):385-395. doi: 10.1016/j.tcb.2019.02.005. Epub 2019 Mar 6.
The Hedgehog (Hh) family of morphogens direct cell fate decisions during embryogenesis and signal to maintain tissue homeostasis after birth. Hh ligands harbor dual lipid modifications that anchor the proteins into producing cell membranes, effectively preventing ligand release. The transporter-like protein Dispatched (Disp) functions to release these membrane tethers and mobilize Hh ligands to travel toward distant cellular targets. The molecular mechanisms by which Disp achieves Hh deployment are not yet fully understood, but a number of recent publications provide insight into the complex process of Hh release. Herein we review this literature, integrate key discoveries, and discuss some of the open questions that will drive future studies aimed at understanding Disp-mediated Hh ligand deployment.
刺猬(Hh)家族的形态发生素在胚胎发生过程中指导细胞命运决定,并发出信号以维持出生后的组织内稳态。Hh 配体具有双重脂质修饰,将蛋白质锚定在产生细胞膜中,有效地防止配体释放。转运蛋白样蛋白 Dispatched(Disp)的功能是释放这些膜束缚物,并动员 Hh 配体向远处的细胞靶标移动。Disp 实现 Hh 部署的分子机制尚未完全了解,但最近的一些出版物提供了对 Hh 释放这一复杂过程的深入了解。本文综述了这一文献,整合了关键发现,并讨论了一些悬而未决的问题,这些问题将推动未来旨在了解 Disp 介导的 Hh 配体部署的研究。