TMEM132A regulates Wnt/β-catenin signaling through stabilizing LRP6 during mouse embryonic development.

IF 8.2 2区生物学 Q1 CELL BIOLOGY

Cell Communication and Signaling Pub Date : 2024-10-09 DOI:10.1186/s12964-024-01855-9

Shin Ae Oh, Jiyeon Jeon, Su-Yeon Je, Seoyoung Kim, Joohyun Jung, Hyuk Wan Ko

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引用次数: 0

Abstract

The Wnt/β-catenin signaling pathway is crucial for embryonic development and adult tissue homeostasis. Dysregulation of Wnt signaling is linked to various developmental anomalies and diseases, notably cancer. Although numerous regulators of the Wnt signaling pathway have been identified, their precise function during mouse embryo development remains unclear. Here, we revealed that TMEM132A is a crucial regulator of canonical Wnt/β-catenin signaling in mouse development. Mouse embryos lacking Tmem132a displayed a range of malformations, including open spina bifida, caudal truncation, syndactyly, and renal defects, similar to the phenotypes of Wnt/β-catenin mutants. Tmem132a knockdown in cultured cells suppressed canonical Wnt/β-catenin signaling. In developing mice, loss of Tmem132a also led to diminished Wnt/β-catenin signaling. Mechanistically, we showed that TMEM132A interacts with the Wnt co-receptor LRP6, thereby stabilizing it and preventing its lysosomal degradation. These findings shed light on a novel role for TMEM132A in regulating LRP6 stability and canonical Wnt/β-catenin signaling during mouse embryo development. This study provides valuable insights into the molecular intricacies of the Wnt signaling pathway. Further research may deepen our understanding of Wnt pathway regulation and offer its potential therapeutic applications.

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在小鼠胚胎发育过程中，TMEM132A通过稳定LRP6调节Wnt/β-catenin信号。

Wnt/β-catenin信号通路对胚胎发育和成体组织稳态至关重要。Wnt 信号传导失调与各种发育异常和疾病（尤其是癌症）有关。虽然已经发现了许多 Wnt 信号通路的调节因子，但它们在小鼠胚胎发育过程中的确切功能仍不清楚。在这里，我们发现 TMEM132A 是小鼠发育过程中典型 Wnt/β-catenin 信号传导的关键调节因子。缺乏Tmem132a的小鼠胚胎表现出一系列畸形，包括开放性脊柱裂、尾骨截断、联合畸形和肾脏缺陷，与Wnt/β-catenin突变体的表型相似。在培养细胞中敲除Tmem132a抑制了典型的Wnt/β-catenin信号传导。在发育中的小鼠中，Tmem132a的缺失也会导致Wnt/β-catenin信号的减弱。从机理上讲，我们发现 TMEM132A 与 Wnt 共受体 LRP6 相互作用，从而稳定 LRP6 并阻止其溶酶体降解。这些发现揭示了TMEM132A在小鼠胚胎发育过程中调节LRP6稳定性和典型Wnt/β-catenin信号传导的新作用。这项研究为我们深入了解 Wnt 信号通路的分子复杂性提供了宝贵的见解。进一步的研究可能会加深我们对Wnt通路调控的理解，并提供其潜在的治疗应用。

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来源期刊

Cell Communication and Signaling CELL BIOLOGY-

CiteScore

11.00

自引率

0.00%

发文量

180

期刊介绍： Cell Communication and Signaling (CCS) is a peer-reviewed, open-access scientific journal that focuses on cellular signaling pathways in both normal and pathological conditions. It publishes original research, reviews, and commentaries, welcoming studies that utilize molecular, morphological, biochemical, structural, and cell biology approaches. CCS also encourages interdisciplinary work and innovative models, including in silico, in vitro, and in vivo approaches, to facilitate investigations of cell signaling pathways, networks, and behavior. Starting from January 2019, CCS is proud to announce its affiliation with the International Cell Death Society. The journal now encourages submissions covering all aspects of cell death, including apoptotic and non-apoptotic mechanisms, cell death in model systems, autophagy, clearance of dying cells, and the immunological and pathological consequences of dying cells in the tissue microenvironment.