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Role of the Ror family receptors in Wnt5a signaling

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Abstract

Ror-family receptors, Ror1 and Ror2, are type I transmembrane proteins that possess an extracellular cysteine-rich domain, which is conserved throughout the Frizzled-family receptors and is a binding site for Wnt ligands. Both Ror1 and Ror2 function primarily as receptors or co-receptors for Wnt5a to activate the β-catenin-independent, non-canonical Wnt signaling, thereby regulating cell polarity, migration, proliferation, and differentiation depending on the context. Ror1 and Ror2 are expressed highly in many tissues during embryogenesis but minimally or scarcely in adult tissues, with some exceptions. In contrast, Ror1 and Ror2 are expressed in many types of cancers, and their high expression often contributes to the progression of the disease. Therefore, Ror1 and Ror2 have been proposed as potential targets for the treatment of the malignancies. In this review, we provide an overview of the regulatory mechanisms of Ror1/Ror2 expression and discuss how Wnt5a-Ror1/Ror2 signaling is mediated and regulated by their interacting proteins.

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Acknowledgements

This work was supported in part by grants from JST Moonshot R&D [JPMJMS2022 (Y.M.)], the Japan Agency for Medical Research and Development (AMED) [18gm5010001s0901 (Y.M.)], and MEXT/JSPS KAKENHI [21K15504 (K.K.); 23K06678 (M.N.)].

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  1. Division of Cell Physiology, Department of Physiology and Cell Biology, Graduate School of Medicine, Kobe University, Kobe, 650-0017, Japan

    Koki Kamizaki & Yasuhiro Minami

  2. Department of Biochemistry, Fukushima Medical University School of Medicine, 1 Hikariga-Oka, Fukushima, 960-1295, Japan

    Michiru Nishita

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  1. Koki Kamizaki
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Kamizaki, K., Minami, Y. & Nishita, M. Role of the Ror family receptors in Wnt5a signaling. In Vitro Cell.Dev.Biol.-Animal (2024). https://doi.org/10.1007/s11626-024-00885-4

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