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

被引：2

作者：

Oh, Shin Ae ^{[1
,2
]}

Jeon, Jiyeon ^{[1
,2
]}

Je, Su-yeon ^{[1
,2
]}

Kim, Seoyoung ^{[1
,2
]}

Jung, Joohyun ^{[1
]}

Ko, Hyuk Wan ^{[1
]}

机构：

[1] Yonsei Univ, Coll Life Sci & Biotechnol, Dept Biochem, Seoul 03722, South Korea

[2] Yonsei Univ, Yonsei Educ & Res Ctr Biosyst, Brain Korea 21 BK21 FOUR Program, Seoul 03722, South Korea

来源：

CELL COMMUNICATION AND SIGNALING | 2024年 / 22卷 / 01期

基金：

新加坡国家研究基金会;

关键词：

TMEM132A; Wnt/beta-catenin signaling; LRP6; Mouse development; Lysosomal degradation; PLANAR-CELL-POLARITY; WNT; ASSOCIATION; INITIATION;

D O I：

10.1186/s12964-024-01855-9

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The Wnt/beta-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/beta-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/beta-catenin mutants. Tmem132a knockdown in cultured cells suppressed canonical Wnt/beta-catenin signaling. In developing mice, loss of Tmem132a also led to diminished Wnt/beta-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/beta-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.

引用

页数：11

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