Disease relevance of Arf6

• To determine whether ARF6 is involved in insulin-regulated exocytosis, 3T3-L1 adipocytes were infected with recombinant adenovirus expressing wild-type ARF6 or an ARF6 dominant negative mutant (D125N) that encodes a protein with nucleotide specificity modified from guanine to xanthine [1].

High impact information on Arf6

• PIP2 formation is regulated by Arf6 [2].
• This reduction in PIP2 occurred in spite of fact that PIP5K appeared to be recruited efficiently to the site of bacterial binding, indicating a role for Arf6 in activation of the kinase [2].
• V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the protein degradative pathway [3].
• A dominant-negative mutant of ARF6 (T27N mutation) dramatically affected FcR-mediated phagocytosis [4].
• Here, we report that endogenous ADP ribosylation factor 6 (ARF6), a small GTP-binding protein, undergoes a sharp and transient activation in macrophages when phagocytosis was initiated via receptors for the Fc portion of immunoglobulins (FcRs) [4].

Biological context of Arf6

• Livers from ARF6-/- embryos are smaller and exhibit hypocellularity, due to the onset of midgestational liver cell apoptosis [5].
• The mammalian small GTPase ADP-ribosylation factor 6 (ARF6) plays important roles in a wide variety of cellular events, including endocytosis, actin cytoskeletal reorganization, and phosphoinositide metabolism [5].

Anatomical context of Arf6

• Forced expression of TRE17 promotes the localization of Arf6 to the plasma membrane, leading to Arf6 activation, presumably due to facilitated access to membrane-associated guanine nucleotide exchange factors (GEFs) [6].
• Collectively, these data implicate both Arf6 and Rab11 as crucial mediators of constitutive and insulin-stimulated secretion of ACRP30 and further suggest that recycling endosomes may play a central role in this process [7].
• ADP ribosylation factor 6 is activated and controls membrane delivery during phagocytosis in macrophages [4].
• Expression of a dominant-inhibitory ARF6 mutant, ARF6(T27N), impaired glucose-, depolarization-, and gamma-thio-GTP-stimulated insulin secretion in the pancreatic beta cell line, MIN6 [8].
• The GTP-binding protein ADP-ribosylation factor 6 (Arf6) regulates endosomal membrane trafficking and the actin cytoskeleton in the cell periphery [9].

Associations of Arf6 with chemical compounds

• ADP-ribosylation factor 6 regulates insulin secretion through plasma membrane phosphatidylinositol 4,5-bisphosphate [8].
• ADP-ribosylation factor 6 delineates separate pathways used by endothelin 1 and insulin for stimulating glucose uptake in 3T3-L1 adipocytes [10].
• These results indicate a requirement for ARF6 in basal and insulin-regulated adipsin secretion but not in glucose transport [1].
• In contrast, the secretion of adipsin, a serine protease specifically expressed in adipocytes, was increased by the expression of wild-type ARF6 and was inhibited by the expression of D125N [1].

Other interactions of Arf6

• We also demonstrate that Arf6 also plays a role in the secretion of ACRP30 [7].
• Here we investigated whether the small GTPase, ADP-ribosylation factor 6 (ARF6), which regulates actin dynamics and peripheral vesicular trafficking, is involved in the regulation of spine formation [11].

Analytical, diagnostic and therapeutic context of Arf6

• In situ hybridization histochemistry revealed that EFA6C mRNA was expressed predominantly in mature Purkinje cells and the epithelial cells of the choroid plexus in contrast to the ubiquitous expression of ARF6 mRNA throughout the brain [12].

References