Models for the functions of Arf GAPs - PubMed (original) (raw)

Review

Models for the functions of Arf GAPs

Michael P East et al. Semin Cell Dev Biol. 2011 Feb.

Abstract

Arf GAPs (ADP-ribosylation factor GTPase-activating proteins) are essential components of Arf (ADP-ribosylation factor) signaling pathways. Arf GAPs stimulate the hydrolysis of GTP to GDP to transition Arf from the active, GTP bound, state to the inactive, GDP bound, state. Based on this activity, Arf GAPs were initially proposed to function primarily or exclusively as terminators of Arf signaling. Further studies of Arf GAPs have revealed that they also function as effectors of Arf signaling in at least a few steps or processes in which Arfs are not directly involved. In this review we discuss the non-canonical functions of Arf GAPs and address several key questions in the field, including: whether (1) Arf GAPs are terminators or effectors of Arf signaling, (2) Arf GAPs positively or negatively regulate COPI assembly, (3) Arf GAPs are involved in vesicle fission, and (4) Arf GAPs regulate vesicle uncoating.

Copyright © 2010 Elsevier Ltd. All rights reserved.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Model of Arf GAP functions in Arf-dependent signaling and termination. The GTP cycle of Arf depends upon Arf GEFs to facilitate the exchange of bound GDP for GTP and Arf GAPs to stimulate hydrolysis of GTP to GDP. GTP binding by Arf induces a conformational change that increases the affinity of Arf for effector proteins ultimately leading to a biological response, mediated by effectors. As discussed in the text, association with Arf GAPs or with Arf GAP/effector complexes also results in biological responses, suggesting that Arf GAPs can serve as Arf effectors. Thus, Arf GAPs have at least dual roles in regulating Arf signaling as terminators and effectors. This conclusion also points to the regulation of Arf GAP activity as a critical, yet understudied, aspect of Arf and Arf GAP signaling.

Similar articles

Cited by

References

    1. Kahn RA, Cherfils J, Elias M, Lovering RC, Munro S, Schurmann A. Nomenclature for the human Arf family of GTP-binding proteins: ARF, ARL, and SAR proteins. J Cell Biol. 2006;172:645–50. - PMC - PubMed
    1. Kahn RA. Toward a model for Arf GTPases as regulators of traffic at the Golgi. FEBS Lett. 2009;583:3872–9. - PMC - PubMed
    1. Kahn RA, Gilman AG. The protein cofactor necessary for ADP-ribosylation of Gs by cholera toxin is itself a GTP binding protein. J Biol Chem. 1986;261:7906–11. - PubMed
    1. Cukierman E, Huber I, Rotman M, Cassel D. The ARF1 GTPase-activating protein: zinc finger motif and Golgi complex localization. Science. 1995;270:1999–2002. - PubMed
    1. Kahn RA, Bruford E, Inoue H, Logsdon JM, Jr, Nie Z, Premont RT, et al. Consensus nomenclature for the human ArfGAP domain-containing proteins. J Cell Biol. 2008;182:1039–44. - PMC - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources