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

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

  • EMBO Rep. 2024 Nov;25(11):5053-5079. doi: 10.1038/s44319-024-00289-1.
Yuan Gao # 1 2,  Jing Feng # 1 2,  Yansong Zhang 1 2 3,  Mengyuan Yi 1,  Lebing Zhang 1 2,  Yan Yan 4,  Alan Jian Zhu 5 6 7,  Min Liu 8 9
Affiliations

Affiliations

  • 1 Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing, 100871, China.
  • 2 Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
  • 3 Peking University Chengdu Academy for Advanced Interdisciplinary Biotechnologies, Chengdu, Sichuan, 610213, China.
  • 4 Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
  • 5 Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing, 100871, China. zhua@pku.edu.cn.
  • 6 Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China. zhua@pku.edu.cn.
  • 7 Peking University Chengdu Academy for Advanced Interdisciplinary Biotechnologies, Chengdu, Sichuan, 610213, China. zhua@pku.edu.cn.
  • 8 Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing, 100871, China. liumin02@pku.edu.cn.
  • 9 Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China. liumin02@pku.edu.cn.
  • # Contributed equally.
PMID: 39402333 DOI: 10.1038/s44319-024-00289-1
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.

Keywords

AP-1; Ehbp1; Wg/Wnt; Wls.

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