title: FYCO1 is a Rab7 effector that binds to LC3 and PI3P to mediate microtubule plus end-directed vesicle transport.
abstract: Autophagy is the main eukaryotic degradation pathway for long-lived proteins, protein aggregates, and cytosolic organelles. Although the protein machinery involved in the biogenesis of autophagic vesicles is well described, very little is known about the mechanism of cytosolic transport of autophagosomes. In this study, we have identified an adaptor protein complex, formed by the two autophagic membrane-associated proteins LC3 and Rab7 and the novel FYVE and coiled-coil (CC) domain-containing protein FYCO1, that promotes microtubule (MT) plus end-directed transport of autophagic vesicles. We have characterized the LC3-, Rab7-, and phosphatidylinositol-3-phosphate-binding domains in FYCO1 and mapped part of the CC region essential for MT plus end-directed transport. We also propose a mechanism for selective autophagosomal membrane recruitment of FYCO1.
authors.affiliation: Molecular Cancer Research Group, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway.
authors.forename: Serhiy
authors.initials: S
authors.lastname: Pankiv
authors.forename: Endalkachew A
authors.initials: EA
authors.lastname: Alemu
authors.forename: Andreas
authors.initials: A
authors.lastname: Brech
authors.forename: Jack-Ansgar
authors.initials: JA
authors.lastname: Bruun
authors.forename: Trond
authors.initials: T
authors.lastname: Lamark
authors.forename: Aud
authors.initials: A
authors.lastname: Overvatn
authors.forename: Geir
authors.initials: G
authors.lastname: Bjørkøy
authors.forename: Terje
authors.initials: T
authors.lastname: Johansen
mesh_terms: D001343:Autophagy / Q000502:physiology; D001665:Binding Sites / Q000502:physiology; D001693:Biological Transport, Active / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D022161:Transport Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000090802:rab7 GTP-Binding Proteins
chemical_list: D004268:DNA-Binding Proteins; C460141:FYCO1 protein, human; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D018129:Phosphatidylinositol Phosphates; D014157:Transcription Factors; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; D020691:rab GTP-Binding Proteins