title: Regulation of cargo-selective endocytosis by dynamin 2 GTPase-activating protein girdin.
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.
authors: Department of Pathology, Nagoya University Graduate School of Medicine, Showa-ku Nagoya, Japan.
authors: Liang
authors: L
authors: Weng
authors: Department of Pathology, Nagoya University Graduate School of Medicine, Showa-ku Nagoya, Japan enomoto@iar.nagoya-u.ac.jp mtakaha@med.nagoya-u.ac.jp.
authors: Atsushi
authors: A
authors: Enomoto
authors: Department of Microbiology, St. Marianna University School of Medicine, Miyamae Kawasaki, Japan.
authors: Hiroshi
authors: H
authors: Miyoshi
authors: Department of Neuropsychiatry, St. Marianna University School of Medicine, Miyamae Kawasaki, Japan.
authors: Kiyofumi
authors: K
authors: Takahashi
authors: Department of Pathology, Nagoya University Graduate School of Medicine, Showa-ku Nagoya, Japan.
authors: Naoya
authors: N
authors: Asai
authors: Institute for Integrated Cell-Material Sciences, Kyoto University, Sakyo-ku Kyoto, Japan.
authors: Nobuhiro
authors: N
authors: Morone
authors: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics Ministry of Health, Dong Dan Beijing, China.
authors: Ping
authors: P
authors: Jiang
authors: Department of Respiratory Medicine, Xiangya Hospital Central South University, Kaifu District Changsha, China.
authors: Jian
authors: J
authors: An
authors: Department of Pathology, Nagoya University Graduate School of Medicine, Showa-ku Nagoya, Japan.
authors: Takuya
authors: T
authors: Kato
authors: Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Showa-ku Nagoya, Japan.
authors: Keisuke
authors: K
authors: Kuroda
authors: Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Showa-ku Nagoya, Japan.
authors: Takashi
authors: T
authors: Watanabe
authors: Department of Pathology, Nagoya University Graduate School of Medicine, Showa-ku Nagoya, Japan.
authors: Masato
authors: M
authors: Asai
authors: Department of Pathology, Nagoya University Graduate School of Medicine, Showa-ku Nagoya, Japan.
authors: Maki
authors: M
authors: Ishida-Takagishi
authors: Department of Pathology, Kitasato University School of Medicine, Minami-ku Sagamihara, Japan.
authors: Yoshiki
authors: Y
authors: Murakumo
authors: Department of Microbiology, St. Marianna University School of Medicine, Miyamae Kawasaki, Japan.
authors: Hideki
authors: H
authors: Nakashima
authors: Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Showa-ku Nagoya, Japan.
authors: Kozo
authors: K
authors: Kaibuchi
authors: Department of Pathology, Nagoya University Graduate School of Medicine, Showa-ku Nagoya, Japan enomoto@iar.nagoya-u.ac.jp mtakaha@med.nagoya-u.ac.jp.
authors: Masahide
authors: M
authors: Takahashi
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D034285:Dynamin II / Q000378:metabolism*; D004705:Endocytosis; D004847:Epithelial Cells / Q000502:physiology*; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: C502451:CCDC88A protein, human; D020690:GTPase-Activating Proteins; D008840:Microfilament Proteins; D033921:Vesicular Transport Proteins; D034285:Dynamin II
keywords: GTPase‐activating protein; clathrin‐mediated endocytosis; dynamin; girdin; selective endocytosis