Regulation of cargo-selective endocytosis by dynamin 2 GTPase-activating protein girdin

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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17 Citations (Scopus)

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. Synopsis The actin binding protein girdin is a GAP for dynamin 2. Girdin regulates clathrin-dependent endocytosis through a non-canonical mechanism that involves competition between dynamin 2 and certain cargos for girdin binding, resulting in spatial control of protein internalization. The actin-binding protein girdin is a GAP for dynamin 2 involved in clathrin-dependent endocytosis. Girdin inhibits endocytosis of certain cargos but is required for others at the center but not the periphery of the cell. Competitive interaction between cargoes and dynamin 2 for girdin binding is involved in the selective endocytosis. The actin binding protein girdin is a GAP for dynamin 2. Girdin regulates clathrin-dependent endocytosis through a non-canonical mechanism that involves competition between dynamin 2 and certain cargos for girdin binding, resulting in spatial control of protein internalization.

Original languageEnglish
Pages (from-to)2098-2112
Number of pages15
JournalEMBO Journal
Volume33
Issue number18
DOIs
Publication statusPublished - 2014 Sep 17
Externally publishedYes

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Keywords

  • clathrin-mediated endocytosis
  • dynamin
  • girdin
  • GTPase-activating protein
  • selective endocytosis

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Medicine(all)

Cite this

Weng, L., Enomoto, A., Miyoshi, H., Takahashi, K., Asai, N., Morone, N., Jiang, P., An, J., Kato, T., Kuroda, K., Watanabe, T., Asai, M., Ishida-Takagishi, M., Murakumo, Y., Nakashima, H., Kaibuchi, K., & Takahashi, M. (2014). Regulation of cargo-selective endocytosis by dynamin 2 GTPase-activating protein girdin. EMBO Journal, 33(18), 2098-2112. https://doi.org/10.15252/embj.201488289