Map7/7D1 and Dvl form a feedback loop that facilitates microtubule remodeling and Wnt5a signaling |
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| Authors: | Koji Kikuchi Akira Nakamura Masaki Arata Dongbo Shi Mami Nakagawa Tsubasa Tanaka Tadashi Uemura Toshihiko Fujimori Akira Kikuchi Akiyoshi Uezu Yasuhisa Sakamoto Hiroyuki Nakanishi |
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| Affiliation: | 1. Department of Molecular Pharmacology, Graduate School of Medical Sciences, Kumamoto University, Chuo‐ku, Kumamoto, Japan;2. Department of Germline Development, Institute of Molecular Embryology and Genetics, Kumamoto University, Chuo‐ku, Kumamoto, Japan;3. Graduate School of Pharmaceutical Sciences, Kumamoto University, Chuo‐ku, Kumamoto, Japan;4. Graduate School of Biostudies, Kyoto University, Sakyo‐ku, Kyoto, Japan;5. Division of Embryology, National Institute for Basic Biology, Okazaki, Aichi, Japan;6. Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan |
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| Abstract: | The Wnt signaling pathway can be grouped into two classes, the β‐catenin‐dependent and β‐catenin‐independent pathways. Wnt5a signaling through a β‐catenin‐independent pathway promotes microtubule (MT) remodeling during cell‐substrate adhesion, cell migration, and planar cell polarity formation. Although Wnt5a signaling and MT remodeling are known to form an interdependent regulatory loop, the underlying mechanism remains unknown. Here we show that in HeLa cells, the paralogous MT‐associated proteins Map7 and Map7D1 (Map7/7D1) form an interdependent regulatory loop with Disheveled, the critical signal transducer in Wnt signaling. Map7/7D1 bind to Disheveled, direct its cortical localization, and facilitate the cortical targeting of MT plus‐ends in response to Wnt5a signaling. Wnt5a signaling also promotes Map7/7D1 movement toward MT plus‐ends, and depletion of the Kinesin‐1 member Kif5b abolishes the Map7/7D1 dynamics and Disheveled localization. Furthermore, Disheveled stabilizes Map7/7D1. Intriguingly, Map7/7D1 and its Drosophila ortholog, Ensconsin show planar‐polarized distribution in both mouse and fly epithelia, and Ensconsin influences proper localization of Drosophila Disheveled in pupal wing cells. These results suggest that the role of Map7/7D1/Ensconsin in Disheveled localization is evolutionarily conserved. |
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| Keywords: | Disheveled Kinesin‐1 microtubule remodeling microtubule‐associated proteins β ‐catenin‐independent Wnt5a signaling |
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