Arf Family

Abstract

Arfs or adenosine diphosphate (ADP)-ribosylation factors are highly conserved 20-kDa guanine nucleotide-binding proteins found in all eukaryotic cells from Giardia, the most primitive existing eukaryote, to primates. No Arfs have been identified in prokaryotes, which lack membranous organelles and intracellular vesicular trafficking. Arfs have critical roles in multiple cellular functions, including protein secretion, cytoskeletal rearrangement, and signal transduction (e.g., responses to insulin and epidermal growth factor). Members of the Arf family and their regulators are just beginning to be implicated in diseases and pathological processes such as metastasis. Vesicular trafficking and signal transduction in eukaryotes are required for intracellular communication and cargo transport among organelles, as well as in extra- or intercellular functions. Membrane trafficking involves the formation, translocation, and fusion of vesicles of defined structure and molecular composition, initiated at specified intracellular membrane sites for movement of diverse cargo and membrane molecules to appropriate targets or docking membrane sites, beginning with deformation (budding) of the donor membrane with assembly of protein and lipid molecules for vesicle maturation. Finally, vesicle release by fission, translocation, tethering at its destination, followed by uncoating, and fusion with the target membrane, completes a step in vesicular transport. The investigation of Arf actions has contributed significantly to understanding many of those events at a molecular level. Information regarding human ARF6 function of actin cytoskeleton and membrane dynamics, which is relevant to cancer development and potential involvement of individual Arf protein actions, continues to grow, although mechanisms of trafficking in endoplasmic reticulum and Golgi compartments are probably still understood better and in more detail.