title: SGIP1alpha is an endocytic protein that directly interacts with phospholipids and Eps15.
abstract: SGIP1 has been shown to be an endophilin-interacting protein that regulates energy balance, but its function is not fully understood. Here, we identified its splicing variant of SGIP1 and named it SGIP1alpha. SGIP1alpha bound to phosphatidylserine and phosphoinositides and deformed the plasma membrane and liposomes into narrow tubules, suggesting the involvement in vesicle formation during endocytosis. SGIP1alpha furthermore bound to Eps15, an important adaptor protein of clathrin-mediated endocytic machinery. SGIP1alpha was colocalized with Eps15 and the AP-2 complex. Upon epidermal growth factor (EGF) stimulation, SGIP1alpha was colocalized with EGF at the plasma membrane, indicating the localization of SGIP1alpha at clathrin-coated pits/vesicles. SGIP1alpha overexpression reduced transferrin and EGF endocytosis. SGIP1alpha knockdown reduced transferrin endocytosis but not EGF endocytosis; this difference may be due to the presence of redundant pathways in EGF endocytosis. These results suggest that SGIP1alpha plays an essential role in clathrin-mediated endocytosis by interacting with phospholipids and Eps15.
authors.affiliation: Department of Molecular Pharmacology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Uezu
authors.forename: Ayaka
authors.initials: A
authors.lastname: Horiuchi
authors.forename: Kousuke
authors.initials: K
authors.lastname: Kanda
authors.forename: Naoya
authors.initials: N
authors.lastname: Kikuchi
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Umeda
authors.forename: Kazuya
authors.initials: K
authors.lastname: Tsujita
authors.forename: Shiro
authors.initials: S
authors.lastname: Suetsugu
authors.forename: Norie
authors.initials: N
authors.lastname: Araki
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Tadaomi
authors.initials: T
authors.lastname: Takenawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakanishi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D017398:Alternative Splicing / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D022163:Clathrin-Coated Vesicles / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis; D004734:Energy Metabolism / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D010743:Phospholipids / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D050656:Transcription Factor AP-2 / Q000235:genetics / Q000378:metabolism; D014168:Transferrin / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; C486206:EPS15 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010743:Phospholipids; D010750:Phosphoproteins; D020033:Protein Isoforms; C523897:SGIP1 protein, human; C107640:SH3GL2 protein, human; D050656:Transcription Factor AP-2; D014168:Transferrin; D004815:Epidermal Growth Factor