ADP-Ribosylation Factors (ARF)

DefinitionARFs function both constitutively within the
Adenosine diphosphate-ribosylation factor (ARF)secretory pathway and as targets of signal
proteins are members of the GTP-binding proteins oftransduction in the cell periphery1. ARF proteins
the Ras superfamily1. They are major regulators offunction in the regulation of membrane traffic and
vesicle biogenesis in intracellular traffic, lipidthe organization of the cytoskeleton that are crucial
metabolism, microtubule dynamics, development andto fundamental cellular processes, such as intracellular
other cellular processes2.sorting/trafficking of newly synthesized proteins and
Discoveryendocytosis/exocytosis. They act at membrane
ARF was originally identified as a cofactor for cholerasurfaces to modify lipid composition and to recruit
toxin A catalyzed ADP-ribosylation of the stimulatorycoat proteins for the generation of transport
GTP-binding component of adenylate cyclase3.vesicles5. ARF proteins play a key regulatory role in
Classificationthe remodeling of actin cytoskeleton necessary for
The mammalian ARFs can be grouped into threethe formation of membrane ruffles and protrusions in
classes on the basis of their size and sequenceassociation with phospholipase D and members of the
identity. ARF1, ARF2 and ARF3 are grouped underRho GTPase family. These activities of ARF proteins
class I, ARF4 and ARF5 under class II and ARF6influence the formation, stability and functional
under class III4.integrity of epithelial junctions6.
Structural CharacteristicsReferences
ARFs contain consensus amino acid sequences1. Randazzo PA, Nie Z, Miura K, and Hsu VW, (2000).
involved in GTP binding and hydrolysis whichMolecular Aspects of the Cellular Activities of
determine their catalytic activity3. They contain twoADP-Ribosylation Factors. Sci. STKE, 2000 (59)
switch regions, which change relative positions2. Pasqualato S, Renault L, Cherfils J (2002). Arf, Arl,
between cycles of GDP/GTP-binding. They are similarArp and Sar proteins: a family of GTP-binding proteins
to heterotrimeric G protein subunits, these peptideswith a structural device for 'front-back'
are frequently myristoylated in their N-terminal region,communication. EMBO Rep, 3(11):1035-41.
which contributes to their membrane association.3. Kahn RA and Gilman AG (1984). Purification of a
Mode of actionprotein cofactor required for ADP-ribosylation of the
The controlled binding and hydrolysis of GTP is criticalstimulatory regulatory component of adenylate
to ARF function. ARF proteins cycle betweencyclase by cholera toxin. J. Biol. Chem, 259,
GDP-bound, inactive and GTP-bound, active forms,6228-6234.
and the cycling is regulated by specific guanine4. Moss J and Vaughan M (1995). Structure and
nucleotide releasing factors (GEPs) andFunction of ARF Proteins: Activators of Cholera Toxin
GTPase-activating protein (GAPs). GTPase activatingand Critical Components of Intracellular Vesicular
proteins (GAPs) hydrolyze bound GTP to GDP, andTransport Processes. The American Society for
guanine nucleotide exchange factors adopt a newBiochemistry and Molecular Biology, 270(21):
GTP molecule in place of a bound GDP. The GTP12327-12330.
hydrolysis is required in many secretory pathways like5. Donaldson JG (2008). Arfs and membrane lipids:
formation and docking of vesicles at varioussensing, generating and responding to membrane
membranes. It affects membrane traffic by recruitingcurvature. Biochem J, 414(2):189-94.
coat proteins, including COPI and clathrin adaptor6. Hiroi T (2009). Regulation of epithelial junctions by
complexes to membranes.proteins of the ADP-ribosylation factor family.
Functions