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Review
. 2025 Jan-Mar;108(1):368504241311964.
doi: 10.1177/00368504241311964.

The bidirectional relationship between cilia and PCP signaling pathway core protein Vangl2

Huanyong Qin  1 , Ting Liang  1 , Chuanfen Zhang  1 , Junlin Wu  1 , Xin Sheng  1
Affiliations
Review

The bidirectional relationship between cilia and PCP signaling pathway core protein Vangl2

Huanyong Qin et al. Sci Prog. 2025 Jan-Mar.

Abstract

Vangl2, a core component of the PCP signaling pathway, serves as a scaffold protein on the cell membrane, playing a crucial role in organizing protein complexes. Cilia, dynamic structures on the cell surface, carry out a wide range of functions. Research has highlighted a bidirectional regulatory interaction between Vangl2 and cilia, underscoring their interconnected roles in cellular processes. This relationship is demonstrated by the localization of Vangl2 at the base and proximal regions of cilia, where it plays essential roles in ciliary positioning, asymmetric distribution, and ciliogenesis. In contrast, the absence of cilia can disrupt Vangl2-mediated signal transduction processes. This review offers a narrative review of recent research on Vangl2's function in cilia and examines the regulatory effects of cilia on Vangl2-mediated signaling.

Keywords: Vangl2; WNT/PCP signaling pathway; ciliogenesis; primary cilia.

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Conflict of interest statement

Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Structural organization of Vangl2.
Figure 2.
Figure 2.
The architecture of cilia.
Figure 3.
Figure 3.
The influence of Vangl2 on ciliary polarity. The asymmetric distribution of core component complexes mediated by Vangl2 establishes planar cell polarity (PCP). The signaling of the latter affects the distribution, assembly, and attachment sites of actin, thereby influencing the polarized localization of cilia.
Figure 4.
Figure 4.
The role of Vangl2 in the regulation of ciliogenesis. Vangl2 promotes the disassembly of primary cilia by upregulating DVL2 and enhancing the interaction between DVL2 and KIF2A. Meanwhile, it increases the assembly of primary cilia by downregulating pDVL2 and upregulating the assembly-related proteins BBS8 and IFT88. The balance between these two processes ultimately determines the occurrence of primary cilia.
Figure 5.
Figure 5.
The role of primary cilia in Vangl2-mediated PCP pathway signaling. The abnormal state of cilia affects the expression of Vangl2 at the base, which binds to the signaling proteins Prickle and inversin, resulting in reduced activity of DVL and Dsh. This leads to the suppression of the transmission activity of the planar cell polarity (PCP) signaling pathway.
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