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

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 preci...

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Published in:Cell communication and signaling 2024-10, Vol.22 (1), p.482-11, Article 482
Main Authors: Oh, Shin Ae, Jeon, Jiyeon, Je, Su-Yeon, Kim, Seoyoung, Jung, Joohyun, Ko, Hyuk Wan
Format: Article
Language:English
Subjects:
Animals
beta Catenin - genetics
beta Catenin - metabolism
Embryonic Development - genetics
HEK293 Cells
Humans
Low Density Lipoprotein Receptor-Related Protein-6 - genetics
Low Density Lipoprotein Receptor-Related Protein-6 - metabolism
LRP6
Lysosomal degradation
Membrane Proteins - genetics
Membrane Proteins - metabolism
Mice
Mouse development
Protein Stability
Proteolysis
TMEM132A
Wnt Signaling Pathway
Wnt/β-catenin signaling
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Summary: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.
ISSN:1478-811X
1478-811X
DOI:10.1186/s12964-024-01855-9