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Identification of Fzd9b ubiquitination

ABSTRACT: Wnt signaling is critical for the development and maintenance of many cell lineages, including hematopoietic stem cells (HSCs). Tight regulation of Wnt signals is essential, as overactivation can drive tumorigenesis. Numerous Wnt ligands and Frizzled (Fzd) receptors exist, and the negative regulation of particular Fzd signals is the focus of this study. We previously identified the requirement of Wnt9a-Fzd9b pairing for early HSC proliferation. However, the mechanisms controlling activation and signal termination are unclear. Here, we show that the E3 ubiquitin ligase Trip12 (thyroid hormone receptor interactor 12) targets the third intracellular loop of Fzd9b at K437, promoting lysosomal degradation by destabilizing Fzd9b membrane expression. Our data further indicates that Trip12 is semi-selective for Fzd9b. Trip12-mediated reduction of Fzd9b surface expression dampens Wnt9a/Fzd9b signaling, affecting HSC proliferation in zebrafish. Our findings reveal a receptor-specific regulatory mechanism, with implications for targeted Wnt pathway therapies.

INSTRUMENT(S):

ORGANISM(S): Danio Rerio (zebrafish) (brachydanio Rerio) Helicobacter Pylori J99 (campylobacter Pylori J99)

SUBMITTER: Hyoungjoo Lee

LAB HEAD: Stephanie Grainge

PROVIDER: PXD066969 | Pride | 2025-08-08

REPOSITORIES: Pride

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			Action	DRS
	Fzd9b_Ubi.raw	Raw
	Fzd9b_Ubi.sky	Other
	Fzd9b_Ubi.sky.view	Other
	Fzd9b_Ubi.skyd	Other
	Fzd9b_Ubi.skyl	Other

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