title: Phosphatidic acid induces EHD3-containing membrane tubulation and is required for receptor recycling.
abstract: EHD3 is localized on the tubular structures of early endosomes, and it regulates their trafficking pathway. However, the regulatory mechanism of EHD3-containing tubular structures remains poorly understood. An in vitro liposome co-sedimentation assay revealed that EHD3 interacted with phosphatidic acid through its helical domain and this interaction induced liposomal tubulations. Additionally, inhibiting phosphatidic acid synthesis with diacylglycerol kinase inhibitor or lysophosphatidic acid acyltransferase inhibitor significantly reduced the number of EHD3-containing tubules and impaired their trafficking from early endosomes. These results suggest that EHD3 and phosphatidic acid cooperatively regulate membrane deformation and trafficking from early endosomes.
authors.affiliation: Medical Research Institute, Tokyo Women's Medical University, Japan; Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan; Japan Society for the Promotion of Science, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Henmi
authors.affiliation: Medical Research Institute, Tokyo Women's Medical University, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Oe
authors.affiliation: Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Kono
authors.affiliation: Pathological Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Taguchi
authors.affiliation: Department of Neuroscience, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Takei
authors.affiliation: Medical Research Institute, Tokyo Women's Medical University, Japan. Electronic address: tanabe.kenji@twmu.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Tanabe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D022081:Cell Surface Extensions / Q000378:metabolism*; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008969:Molecular Sequence Data; D010712:Phosphatidic Acids / Q000502:physiology*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D021381:Protein Transport; D022161:Transport Vesicles / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C470993:Ehd3 protein, mouse; D010712:Phosphatidic Acids
keywords: EHD; Endosomes; Membrane tubulation; Phophatidic acid; Receptor recycling