FYCO1 is a Rab7 Effector That Binds to LC3 and PI3P to Mediate Microtubule Plus End-directed Vesicle Transport

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2010 Jan 27

PMID 20100911

Citations 338

Authors

Serhiy Pankiv

Endalkachew A Alemu

Andreas Brech

Jack-Ansgar Bruun

Trond Lamark

Aud Overvatn

Geir Bjorkoy

Terje Johansen

Affiliations

Soon will be listed here.

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.

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References

Nowak J, Archange C, Tardivel-Lacombe J, Pontarotti P, Pebusque M, Vaccaro M . The TP53INP2 protein is required for autophagy in mammalian cells. Mol Biol Cell. 2008; 20(3):870-81. PMC: 2633384. DOI: 10.1091/mbc.e08-07-0671. View

Itoh T, Fujita N, Kanno E, Yamamoto A, Yoshimori T, Fukuda M . Golgi-resident small GTPase Rab33B interacts with Atg16L and modulates autophagosome formation. Mol Biol Cell. 2008; 19(7):2916-25. PMC: 2441679. DOI: 10.1091/mbc.e07-12-1231. View

Pankiv S, Clausen T, Lamark T, Brech A, Bruun J, Outzen H . p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem. 2007; 282(33):24131-45. DOI: 10.1074/jbc.M702824200. View

Reggiori F, Monastyrska I, Shintani T, Klionsky D . The actin cytoskeleton is required for selective types of autophagy, but not nonspecific autophagy, in the yeast Saccharomyces cerevisiae. Mol Biol Cell. 2005; 16(12):5843-56. PMC: 1289426. DOI: 10.1091/mbc.e05-07-0629. View

Monastyrska I, He C, Geng J, Hoppe A, Li Z, Klionsky D . Arp2 links autophagic machinery with the actin cytoskeleton. Mol Biol Cell. 2008; 19(5):1962-75. PMC: 2366845. DOI: 10.1091/mbc.e07-09-0892. View

Simonsen A, Lippe R, Christoforidis S, Gaullier J, Brech A, Callaghan J . EEA1 links PI(3)K function to Rab5 regulation of endosome fusion. Nature. 1998; 394(6692):494-8. DOI: 10.1038/28879. View

Liang C, Lee J, Inn K, Gack M, Li Q, Roberts E . Beclin1-binding UVRAG targets the class C Vps complex to coordinate autophagosome maturation and endocytic trafficking. Nat Cell Biol. 2008; 10(7):776-87. PMC: 2878716. DOI: 10.1038/ncb1740. View

Fader C, Sanchez D, Furlan M, Colombo M . Induction of autophagy promotes fusion of multivesicular bodies with autophagic vacuoles in k562 cells. Traffic. 2007; 9(2):230-50. DOI: 10.1111/j.1600-0854.2007.00677.x. View

Kabeya Y, Mizushima N, Yamamoto A, Oshitani-Okamoto S, Ohsumi Y, Yoshimori T . LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation. J Cell Sci. 2004; 117(Pt 13):2805-12. DOI: 10.1242/jcs.01131. View

10.

Tsukada M, Ohsumi Y . Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett. 1993; 333(1-2):169-74. DOI: 10.1016/0014-5793(93)80398-e. View

11.

Paz Y, Elazar Z, Fass D . Structure of GATE-16, membrane transport modulator and mammalian ortholog of autophagocytosis factor Aut7p. J Biol Chem. 2000; 275(33):25445-50. DOI: 10.1074/jbc.C000307200. View

12.

Wang H, Bedford F, Brandon N, Moss S, Olsen R . GABA(A)-receptor-associated protein links GABA(A) receptors and the cytoskeleton. Nature. 1999; 397(6714):69-72. DOI: 10.1038/16264. View

13.

Kirisako T, Baba M, Ishihara N, Miyazawa K, Ohsumi M, Yoshimori T . Formation process of autophagosome is traced with Apg8/Aut7p in yeast. J Cell Biol. 1999; 147(2):435-46. PMC: 2174223. DOI: 10.1083/jcb.147.2.435. View

14.

Lupas A, Van Dyke M, Stock J . Predicting coiled coils from protein sequences. Science. 1991; 252(5009):1162-4. DOI: 10.1126/science.252.5009.1162. View

15.

Song X, Xu W, Zhang A, Huang G, Liang X, Virbasius J . Phox homology domains specifically bind phosphatidylinositol phosphates. Biochemistry. 2001; 40(30):8940-4. DOI: 10.1021/bi0155100. View

16.

Kirkin V, Lamark T, Sou Y, Bjorkoy G, Nunn J, Bruun J . A role for NBR1 in autophagosomal degradation of ubiquitinated substrates. Mol Cell. 2009; 33(4):505-16. DOI: 10.1016/j.molcel.2009.01.020. View

17.

Rose A, Schraegle S, Stahlberg E, Meier I . Coiled-coil protein composition of 22 proteomes--differences and common themes in subcellular infrastructure and traffic control. BMC Evol Biol. 2005; 5:66. PMC: 1322226. DOI: 10.1186/1471-2148-5-66. View

18.

Xie Z, Nair U, Klionsky D . Atg8 controls phagophore expansion during autophagosome formation. Mol Biol Cell. 2008; 19(8):3290-8. PMC: 2488302. DOI: 10.1091/mbc.e07-12-1292. View

19.

Kim J, Huang W, Stromhaug P, Klionsky D . Convergence of multiple autophagy and cytoplasm to vacuole targeting components to a perivacuolar membrane compartment prior to de novo vesicle formation. J Biol Chem. 2001; 277(1):763-73. PMC: 2754695. DOI: 10.1074/jbc.M109134200. View

20.

Kukimoto-Niino M, Takagi T, Akasaka R, Murayama K, Uchikubo-Kamo T, Terada T . Crystal structure of the RUN domain of the RAP2-interacting protein x. J Biol Chem. 2006; 281(42):31843-53. DOI: 10.1074/jbc.M604960200. View