Disease relevance of Arf1

• Synergistic activation of rat brain phospholipase D by ADP-ribosylation factor and rhoA p21, and its inhibition by Clostridium botulinum C3 exoenzyme [1].
• Studies with pertussis toxin and other agents indicate that mastoparan stimulates PLD2 independently of G(i), ARF-1, protein kinase C, and calcium [2].
• In nuclear lysates from either rat liver or ascites hepatoma AH 7974 cells, the PLD activity was markedly stimulated by a recombinant ADP-ribosylation factor (rARF) in the presence of the guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) and phosphatidylinositol 4, 5-bisphosphate [3].
• Enhanced levels of oleate-dependent and Arf-dependent phospholipase D isoforms in experimental colon cancer [4].

High impact information on Arf1

• We now report that ARF is also required for the binding of the AP-1 adaptor protein of clathrin-coated vesicles to Golgi membranes [5].
• The small GTP-binding protein, ADP-ribosylation factor (ARF), has previously been shown to mediate the binding to Golgi membranes of the coatomer of non-cathrin-coated (COP-coated) vesicles [5].
• Studies of ARF binding to isolated Golgi membranes gave similar results [6].
• Receptor and protein kinase C-mediated regulation of ARF binding to the Golgi complex [6].
• In contrast, PKC downregulation and PKC inhibition abolished the activity of GTP and fluoroaluminae in promoting ARF binding to the Golgi complex [6].

Chemical compound and disease context of Arf1

• The ARF signalling inhibitor brefeldin A, protein tyrosine kinase inhibitors and the Rho-inactivating toxin B of Clostridium difficile blunted alpha(1)AR-induced PLD stimulation and largely reduced the cellular PIP(2) content [7].

Biological context of Arf1

• In rat parotid acinar cells, exocytosis is cAMP-dependent and our findings suggest an interaction of Arf1 with the secretory granules [8].
• Sorting into each vesicle population is Arf-1 and GTP hydrolysis dependent and is inhibited by aluminum and beryllium fluoride [9].
• Peroxisome biogenesis: involvement of ARF and coatomer [10].
• ADP-ribosylation factor (ARF) is a small molecular weight GTP-binding protein (20 kD) and has been implicated in vesicular protein transport [11].
• Brefeldin A (BFA), an inhibitor of the activation of ADP-ribosylation factor proteins, inhibited insulin-dependent production of PA and MAPK phosphorylation [12].

Anatomical context of Arf1

• These results suggest that an Arf1-GBF1-BFA complex is formed and has a longer residence time on Golgi membranes than GBF1 or Arf1 alone [13].
• In some kidney epithelial cells Arf1 but not Arf6 was also targeted to a perinuclear patch, where it colocalized with TGN38, a marker of the trans-Golgi network [14].
• Differential expression and targeting of endogenous Arf1 and Arf6 small GTPases in kidney epithelial cells in situ [14].
• In addition to an essential role of Arf1 in vesicle budding, recent observations suggest a role for Arf6 in calcium-dependent exocytosis in bovine adrenal chromaffin cells [8].
• Binding and functions of ADP-ribosylation factor on mammalian and yeast peroxisomes [15].

Associations of Arf1 with chemical compounds

• Dynamics of GBF1, a Brefeldin A-sensitive Arf1 exchange factor at the Golgi [13].
• The ADP ribosylation factor nucleotide exchange factor ARNO promotes beta-arrestin release necessary for luteinizing hormone/choriogonadotropin receptor desensitization [16].
• Overexpression of ARF1 in stably transfected McA-RH7777 cells increased the secretion of VLDL 2 but not of VLDL 1, which was dependent on the availability of oleic acid [17].
• Inhibition by brefeldin A of a Golgi membrane enzyme that catalyses exchange of guanine nucleotide bound to ARF [18].
• Biochemical as well as immunocytochemical evidence is presented showing that peroxisomes incubated with preparations of bovine brain or rat liver cytosol recruit ADP-ribosylation factor (ARF) and coatomer in a strictly guanosine 5'-O-(3-thiotriphosphate)-dependent manner [10].

Physical interactions of Arf1

• The small GTP-binding protein ADP-ribosylation factor (ARF) has been shown to regulate the interaction of actin and actin-binding proteins with the Golgi apparatus [19].

Regulatory relationships of Arf1

• The role of GTPase-activating protein (GAP) that deactivates ADP-ribosylation factor 1 (ARF1) during the formation of coat protein I (COPI) vesicles has been unclear [20].
• A 150-kDa protein that inhibits phospholipase D (PLD) activity stimulated by ADP-ribosylation factor and phosphatidylinositol 4, 5-bisphosphate (PI(4,5)P2) was previously purified from rat brain [21].

Other interactions of Arf1

• Quantitative Western blotting showed that expression of endogenous Arf1 was 26-180 times higher than Arf6 [14].
• These findings support the idea of an Arf1-activated recruitment of an actin, cortactin and Dyn2 complex that is essential for Golgi function [22].
• IPCEF1 has been reported to interact with ADP-ribosylation factor GTP exchange factors of the cytohesin family and function by modulating the cytohesin 2 activity [23].
• ADP-ribosylation factor-directed GTPase-activating protein. Purification and partial characterization [24].
• Arf-1, a catalytic activator, stimulated PLD1 by enhancing the catalytic constant, kcat [25].

Analytical, diagnostic and therapeutic context of Arf1

• The immunoelectron microscopy experiment confirmed Arf1 is translocated to the secretory granules [26].
• The ARF-dependent nuclear PLD activity was increased in the S-phase of the regenerating rat liver after partial hepatectomy and also was much higher in AH 7974 cells than in the resting rat liver [3].

References