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Ehbp1 协调 Wnt/Wingless 有序地分拣到基底外侧和顶端细胞膜。

Ehbp1 orchestrates orderly sorting of Wnt/Wingless to the basolateral and apical cell membranes.

机构信息

Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing, 100871, China.

Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.

出版信息

EMBO Rep. 2024 Nov;25(11):5053-5079. doi: 10.1038/s44319-024-00289-1. Epub 2024 Oct 14.

DOI:10.1038/s44319-024-00289-1
PMID:39402333
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11549480/
Abstract

Wingless (Wg)/Wnt signaling plays a critical role in both development and adult tissue homeostasis. In the Drosophila larval wing disc epithelium, the orderly delivery of Wg/Wnt to the apical and basal cell surfaces is essential for wing development. Here, we identified Ehbp1 as the switch that dictates the direction of Wg/Wnt polarized intracellular transport: the Adaptor Protein complex 1 (AP-1) delivers Wg/Wnt to the basolateral cell surface, and its sequestration by Ehbp1 redirects Wg/Wnt for apical delivery. Genetic analyses showed that Ehbp1 specifically regulates the polarized distribution of Wg/Wnt, a process that depends on the dedicated Wg/Wnt cargo receptor Wntless. Mechanistically, Ehbp1 competes with Wntless for AP-1 binding, thereby preventing the unregulated basolateral Wg/Wnt transport. Reducing Ehbp1 expression, or removing the coiled-coil motifs within its bMERB domain, leads to basolateral Wg/Wnt accumulation. Importantly, the regulation of polarized Wnt delivery by EHBP1 is conserved in vertebrates. The generality of this switch mechanism for regulating intracellular transport remains to be determined in future studies.

摘要

无翅（Wg）/Wnt 信号在发育和成人组织稳态中都发挥着关键作用。在果蝇幼虫翅盘上皮细胞中，Wg/Wnt 有序地递送到顶端和基底细胞表面对于翅膀发育是必不可少的。在这里，我们确定 Ehbp1 是决定 Wg/Wnt 极化细胞内运输方向的开关：衔接蛋白复合物 1（AP-1）将 Wg/Wnt 递送到基底外侧细胞表面，而 Ehbp1 将其隔离会将 Wg/Wnt 重新导向顶端递送到顶端。遗传分析表明，Ehbp1 特异性调节 Wg/Wnt 的极化分布，这个过程依赖于专门的 Wg/Wnt 货物受体 Wntless。在机制上，Ehbp1 与 Wntless 竞争与 AP-1 的结合，从而防止不受调节的基底外侧 Wg/Wnt 运输。降低 Ehbp1 的表达，或去除其 bMERB 结构域内的卷曲螺旋基序，会导致基底外侧 Wg/Wnt 积累。重要的是，EHBP1 对极化 Wnt 递呈的调节在脊椎动物中是保守的。在未来的研究中，仍需要确定这种用于调节细胞内运输的开关机制的普遍性。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfba/11549480/b4d8650322de/44319_2024_289_Fig12_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfba/11549480/382537a3d810/44319_2024_289_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfba/11549480/0a8857487617/44319_2024_289_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfba/11549480/7900ac6e26f0/44319_2024_289_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfba/11549480/cb12b4159e29/44319_2024_289_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfba/11549480/82b69e0d8fc3/44319_2024_289_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfba/11549480/ed54b330350d/44319_2024_289_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfba/11549480/c083edca13fd/44319_2024_289_Fig8_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfba/11549480/3c55a5a31969/44319_2024_289_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfba/11549480/6d38c19a4469/44319_2024_289_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfba/11549480/0e4943c79974/44319_2024_289_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfba/11549480/b4d8650322de/44319_2024_289_Fig12_ESM.jpg

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