title: Characterization of the EFC/F-BAR domain protein, FCHO2.
abstract: We have previously shown that SGIP1α is an endocytic protein specifically expressed in neural tissues. SGIP1α has a lipid-binding domain called the MP domain, which shows no significant homology to any other domains. In this study, we characterized FCHO2, a protein with a high level of homology to SGIP1α. FCHO2 lacks the MP domain but has another lipid-binding domain, the EFC/F-BAR domain. FCHO2 was ubiquitously expressed. The FCHO2 EFC domain bound to phosphatidylserine and phosphoinositides and deformed the plasma membrane and liposomes into narrow tubes. FCHO2 localized to clathrin-coated pits at the plasma membrane and bound to Eps15, an important adaptor protein in clathrin-mediated endocytosis. FCHO2 knockdown reduced transferrin endocytosis. These results suggest that FCHO2 regulates clathrin-mediated endocytosis through its interactions with membranes and Eps15. These properties of FCHO2 are similar to those of SGIP1α. FCHO2 is likely to be a ubiquitous homologue of SGIP1α. We furthermore found that FCHO2 was subjected to monoubiquitination, and gel filtration analysis showed that FCHO2 formed an oligomer. These new properties might also contribute to the role of FCHO2 in clathrin-mediated endocytosis.
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: 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: Tadaomi
authors.initials: T
authors.lastname: Takenawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakanishi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019556:COS Cells; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002522:Chlorocebus aethiops; D002966:Clathrin / Q000235:genetics / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D050556:Fatty Acid-Binding Proteins; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D050356:Lipid Metabolism / Q000502:physiology; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D050656:Transcription Factor AP-2 / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism; D054875:Ubiquitination / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D002966:Clathrin; C486206:EPS15 protein, human; D050556:Fatty Acid-Binding Proteins; C497032:Fcho2 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D010750:Phosphoproteins; D011506:Proteins; D050656:Transcription Factor AP-2; D014168:Transferrin