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

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2024-11-01 Epub Date: 2024-10-14 DOI:10.1038/s44319-024-00289-1

Yuan Gao, Jing Feng, Yansong Zhang, Mengyuan Yi, Lebing Zhang, Yan Yan, Alan Jian Zhu, Min Liu

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引用次数: 0

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.

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Ehbp1 可将 Wnt/Wingless 有序地分拣到基底侧和顶端细胞膜。

无翅（Wg）/Wnt 信号在发育和成体组织稳态中都起着至关重要的作用。在果蝇幼虫翼盘上皮细胞中，Wg/Wnt向顶端和基底细胞表面的有序传递对翅膀的发育至关重要。在这里，我们发现 Ehbp1 是决定 Wg/Wnt 细胞内极化运输方向的开关：适配蛋白复合物 1（AP-1）将 Wg/Wnt 运送到细胞基外侧表面，而 Ehbp1 对其的螯合作用则将 Wg/Wnt 转向顶端运送。遗传分析表明，Ehbp1能特异性地调节Wg/Wnt的极化分布，这一过程依赖于专用的Wg/Wnt货物受体Wntless。从机理上讲，Ehbp1与Wntless竞争AP-1的结合，从而阻止了不受调控的Wg/Wnt基侧运输。减少 Ehbp1 的表达或移除其 bMERB 结构域中的盘卷基团会导致基底侧 Wg/Wnt 聚集。重要的是，EHBP1 对极化 Wnt 运送的调控在脊椎动物中是保守的。这种调节细胞内转运的开关机制的普遍性还有待今后的研究确定。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

期刊介绍： EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings. The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that: Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels. Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies. Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding. Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts. EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry.