Regulation of cargo‐selective endocytosis by dynamin 2 GTPase‐activating protein girdin |
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| Authors: | Liang Weng Atsushi Enomoto Hiroshi Miyoshi Kiyofumi Takahashi Naoya Asai Nobuhiro Morone Ping Jiang Jian An Takuya Kato Keisuke Kuroda Takashi Watanabe Masato Asai Maki Ishida‐Takagishi Yoshiki Murakumo Hideki Nakashima Kozo Kaibuchi Masahide Takahashi |
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| Institution: | 1. Department of Pathology, Nagoya University Graduate School of Medicine, , Showa‐ku, Nagoya, Japan;2. Department of Microbiology, St. Marianna University School of Medicine, , Miyamae, Kawasaki, Japan;3. Department of Neuropsychiatry, St. Marianna University School of Medicine, , Miyamae, Kawasaki, Japan;4. Institute for Integrated Cell‐Material Sciences, Kyoto University, , Sakyo‐ku, Kyoto, Japan;5. The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, , Dong Dan, Beijing, China;6. Department of Respiratory Medicine, Xiangya Hospital, Central South University, , Kaifu District, Changsha, China;7. Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, , Showa‐ku, Nagoya, Japan;8. Department of Pathology, Kitasato University School of Medicine, , Minami‐ku, Sagamihara, Japan |
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| Abstract: | In clathrin‐mediated endocytosis (CME), specificity and selectivity for cargoes are thought to be tightly regulated by cargo‐specific adaptors for distinct cellular functions. Here, we show that the actin‐binding protein girdin is a regulator of cargo‐selective CME. Girdin interacts with dynamin 2, a GTPase that excises endocytic vesicles from the plasma membrane, and functions as its GTPase‐activating protein. Interestingly, girdin depletion leads to the defect in clathrin‐coated pit formation in the center of cells. Also, we find that girdin differentially interacts with some cargoes, which competitively prevents girdin from interacting with dynamin 2 and confers the cargo selectivity for CME. Therefore, girdin regulates transferrin and E‐cadherin endocytosis in the center of cells and their subsequent polarized intracellular localization, but has no effect on integrin and epidermal growth factor receptor endocytosis that occurs at the cell periphery. Our results reveal that girdin regulates selective CME via a mechanism involving dynamin 2, but not by operating as a cargo‐specific adaptor. |
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| Keywords: | clathrin‐mediated endocytosis dynamin girdin GTPase‐activating protein selective endocytosis |
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