Structure and mechanism of COPI vesicle biogenesis

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Distinct trafficking pathways within the secretory and endocytic systems ensure prompt and precise delivery of specific cargo molecules to different cellular compartments via small vesicular (50–150 nm) and tubular carriers. The COPI vesicular coat is required for retrograde trafficking from the cis-Golgi back to the ER and within the Golgi stack. Recent structural data have been obtained from X-ray crystallographic studies on COPI coat components alone and on COPI subunits in complex with either cargo motifs or Arf1, and from reconstructions of COPI coated vesicles by electron tomography. These studies provide important molecular information and indicate key differences in COPI coat assembly as compared with clathrin-based and COPII-based coats.

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Introduction to the COPI coat

Most vesicles are surrounded by protein coats, which interact with specific membranes [1]; initiate, promote, and/or stabilize curvature through protein interactions [2, 3, 4, 5]; select and capture cargo [6, 7]; and ultimately drive vesicle formation. Heptameric COPI (α/β/β′/ɛ/γ/δ/ζ), or coatomer, is essential [8] in organisms from yeast to humans and is recruited en bloc onto Golgi membranes [9], but is often considered conceptually as the B-subcomplex (α/β′/ɛ) and F-subcomplex (β/δ/γ/ζ).

Dilysine-based cargo binding by the B-subcomplex

Efficient COPI coat assembly depends upon both membrane and cargo binding [9, 11, 31], but a molecular explanation for any sort of cargo recognition by COPI has long proven elusive. COPI sorts a variety of important retrograde and recycling cargoes, including the KDEL/HDEL receptor [36, 37]; SNARE proteins [38, 39] required for fusion in the anterograde and retrograde pathways; p24 family proteins with diphenylalanine motifs (FFxx) [32]; and type I transmembrane proteins bearing linear

F-subcomplex recruitment by Arf1-GTP

The small GTPase, Arf1 (reviewed in [51]), plays a central role in recruiting COPI to Golgi membranes through interactions with the F-subcomplex. Briefly, inactive Arf1-GDP is located in the cytosol. Arf1 becomes active when GDP is replaced with GTP by a guanine nucleotide exchange factor (GEF). In COPI vesicle biogenesis, active Arf1-GTP [52] is first recruited to the Golgi membrane following exposure of a myrisotylated, amphipathic N-terminal helix, and Arf1-GTP subsequently recruits the

Electron microscopy and tomography reveal COPI coat heterogeneity

Two groups have published reconstructions of heptameric COPI: the first used single-particle electron microscopy on native COPI isolated from yeast [15], and the second employed cryo-electron tomography on reconstituted COPI coated vesicles [55••]. Both studies highlight intrinsic heterogeneity in COPI coats, in contrast to clathrin or COPII coats. In the first study, a ‘globular’ F-subcomplex and ‘extended’ B-subcomplex were assigned in the heptameric COPI electron density [15]. The second

A structural perspective of COPI vesicle biogenesis

New structural data (summarized in Table 1), combined with published biochemistry and experiments in yeast and mammalian cells, allow us to form an updated picture of COPI membrane recruitment, cargo binding, and coat polymerization. These data also highlight key differences between COPI-based and clathrin-based or COPII-based coats.

X-ray structures have provided a molecular explanation about how multiple reinforcing interactions enable en bloc recruitment of COPI to Golgi membranes. γ-COP and

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

The author would like to thank David Owen for his insight, support, and encouragement over the years; and David Owen, Todd Graham, Richard Suckling, and Bernard Kelly for helpful discussion and critical comments on the manuscript.

References (59)

  • U. Andag et al.

    Dsl1p an essential component of the Golgi-endoplasmic reticulum retrieval system in yeast, uses the same sequence motif to interact with different subunits of the COPI vesicle coat

    J Biol Chem

    (2003)
  • M.R. Jackson et al.

    Identification of a consensus motif for retention of transmembrane proteins in the endoplasmic reticulum

    EMBO J

    (1990)
  • F.M. Townsley et al.

    The KKXX signal mediates retrieval of membrane proteins from the Golgi to the ER in yeast

    Eur J Cell Biol

    (1994)
  • S. Pääbo et al.

    Structural and functional dissection of an MHC class I antigen-binding adenovirus glycoprotein

    EMBO J

    (1986)
  • P.A. Goepfert et al.

    A sorting motif localizes the foamy virus glycoprotein to the endoplasmic reticulum

    J Virol

    (1997)
  • W. Ma et al.

    Rules for the recognition of dilysine retrieval motifs by coatomer

    EMBO J

    (2013)
  • M. Faini et al.

    The structures of COPI-coated vesicles reveal alternate coatomer conformations and interactions

    Science

    (2012)
  • P.J. Watson et al.

    Gamma-COP appendage domain – structure and function

    Traffic

    (2004)
  • M.G.J. Ford et al.

    Curvature of clathrin-coated pits driven by epsin

    Nature

    (2002)
  • B.J. Peter et al.

    BAR domains as sensors of membrane curvature: the amphiphysin BAR structure

    Science

    (2004)
  • J.L. Gallop et al.

    Mechanism of endophilin N-BAR domain-mediated membrane curvature

    EMBO J

    (2006)
  • J. Zimmerberg et al.

    How proteins produce cellular membrane curvature

    Nat Rev Mol Cell Biol

    (2006)
  • L.M. Traub

    Tickets to ride: selecting cargo for clathrin-regulated internalization

    Nat Rev Mol Cell Biol

    (2009)
  • B.T. Kelly et al.

    Endocytic sorting of transmembrane protein cargo

    Curr Opin Cell Biol

    (2011)
  • R. Duden

    ER-to-Golgi transport: COP I and COP II function (review)

    Mol Membr Biol

    (2003)
  • S. Hara-Kuge et al.

    En bloc incorporation of coatomer subunits during the assembly of COP-coated vesicles

    J Cell Biol

    (1994)
  • T. Kirchhausen

    Clathrin

    Ann Rev Biochem

    (2000)
  • L.M. Traub

    Regarding the amazing choreography of clathrin coats

    PLoS Biol

    (2011)
  • C. Russell et al.

    New insights into the structural mechanisms of the COPII coat

    Traffic

    (2010)
  • Cited by (0)

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