FYCO1 is a Rab7 effector that binds to LC3 and PI3P to mediate microtubule plus end-directed vesicle transport.
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.
Pankiv
Serhiy
S
Molecular Cancer Research Group, Institute of Medical Biology, University of Tromsø, 9037 Tromsø, Norway.
Alemu
Endalkachew A
EA
Brech
Andreas
A
Bruun
Jack-Ansgar
JA
Lamark
Trond
T
Overvatn
Aud
A
Bjørkøy
Geir
G
Johansen
Terje
T
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
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