Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015 Jul;25(7):408-16.
doi: 10.1016/j.tcb.2015.02.005. Epub 2015 Mar 17.

Cargo adaptors: structures illuminate mechanisms regulating vesicle biogenesis

Jon E Paczkowski  1 , Brian C Richardson  1 , J Christopher Fromme  2
Affiliations
Review

Cargo adaptors: structures illuminate mechanisms regulating vesicle biogenesis

Jon E Paczkowski et al. Trends Cell Biol. 2015 Jul.

Abstract

Cargo adaptors sort transmembrane protein cargos into nascent vesicles by binding directly to their cytosolic domains. Recent studies have revealed previously unappreciated roles for cargo adaptors and regulatory mechanisms governing their function. The adaptor protein (AP)-1 and AP-2 clathrin adaptors switch between open and closed conformations that ensure they function at the right place at the right time. The exomer cargo adaptor has a direct role in remodeling the membrane for vesicle fission. Several different cargo adaptors functioning in distinct trafficking pathways at the Golgi are similarly regulated through bivalent binding to the ADP-ribosylation factor 1 (Arf1) GTPase, potentially enabling regulation by a threshold concentration of Arf1. Taken together, these studies highlight that cargo adaptors do more than just adapt cargos.

Keywords: GTPase; cargo adaptor; membrane trafficking; vesicle.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Overview of cargo adaptor localization
Shown is a schematic of the secretory and endocytic pathways of a typical eukaryotic cell, highlighting the trafficking pathways controlled by the major cargo adaptors. Traffic is shown to and from the apical plasma membrane. Traffic to the basolateral membrane appears to rely upon similar adaptors used for traffic to the endo-lysosomal system [9]. The precise pathways controlled by many cargo adaptors, especially regarding endocytosis and the endosomal membrane system, remains a subject of debate. Note that Exomer traffics only ~5% of PM proteins in budding yeast, and there is no homolog of Exomer in metazoans, so the sorting mechanism for the bulk of apical PM proteins remains unresolved. ERGIC denotes the ER-Golgi Intermediate Compartment. See also Table 1.
Figure 2
Figure 2. AP-2 binding to cargo and PI(4,5)P2 membranes triggers recruitment of clathrin
(A) The recent structure of the AP-2 core complex in the closed conformation revealing an autoinhibitory interaction with the clathrin box motif (orange) of the β2 subunit [55]. (B) The structure of the AP-2 core complex in the open conformation demonstrating that the binding site for the clathrin box is no longer present [29], consequently the clathrin box is available to recruit clathrin. (C) Model for activation of AP-2 by binding to cargo and PI(4,5)P2, leading to recruitment of clathrin through the released clathrin box motif [55].
Figure 3
Figure 3. Bivalent binding to the Arf1 GTPase by the AP-1, COPI, and Exomer cargo adaptors
(A) Structural model of the COPI F-subcomplex recruited to the membrane surface by two molecules of Arf1. The Arf1 molecule and portions of the F-subcomplex shown in gray are modeled based on homology to the AP-2 complex, and homology between the β-COP and γ-COP subunits (the observed and modeled Arf1 interactions were confirmed biochemically) [61]. It should be noted that a recent cryo-EM study of the COPI coat suggested that the F-subcomplex may adopt a different conformation than does the AP-2 core [112]. (B) Structural model of the AP-1 core complex recruited to the membrane surface by two molecules of Arf1. The Arf1 molecule shown in gray is modeled based on homology between the β1 and γ subunits (the observed and modeled Arf1 interactions were confirmed biochemically) [71]. (C) Structure of the Exomer/Arf1 complex bound to membranes (all interactions, including with the membrane surface, were confirmed biochemically) [88].
Figure 4
Figure 4. The exomer cargo adaptor remodels the membrane
(A) Normal mode analysis was used to model the hinge motion of the Exomer/Arf1 complex [88]. The hinge motion of the exomer complex has been established [86]. (B) Schematic of the dual roles of exomer in biogenesis of a secretory vesicle: cargo sorting and membrane remodeling. (C) Structural model of several Exomer/Arf1 complexes on the constricted neck of a budding vesicle. One-half of a tangential cross-section of the budding vesicle neck is shown for clarity. The myristoylated N-terminal amphipathic helix of each Arf1 molecule is modeled based on a previous study [90].
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Schekman R, Orci L. Coat proteins and vesicle budding. Science. 1996;271:1526–1533. - PubMed
    1. Bonifacino JS, Glick BS. The mechanisms of vesicle budding and fusion. Cell. 2004;116:153–166. - PubMed
    1. De Matteis MA, Luini A. Exiting the Golgi complex. Nat Rev Mol Cell Biol. 2008;9:273–284. - PubMed
    1. Pucadyil TJ, Schmid SL. Conserved functions of membrane active GTPases in coated vesicle formation. Science. 2009;325:1217–1220. - PMC - PubMed
    1. Donaldson JG, Jackson CL. ARF family G proteins and their regulators: roles in membrane transport, development and disease. Nat Rev Mol Cell Biol. 2011;12:362–375. - PMC - PubMed

Publication types

MeSH terms

Substances