High impact information on Arf6

• Arf6 activation releases docked beta-arrestin necessary for receptor desensitization, providing a feedback mechanism for receptor self-regulation [1].
• We conclude that both activation of ARF6 by antigen and a continual PLD2 activity are essential for local phosphatidylinositol(4,5)bisphosphate generation that regulates dynamic actin cytoskeletal rearrangements [2].
• Quantitative Western blotting showed that expression of endogenous Arf1 was 26-180 times higher than Arf6 [3].
• As a first step in understanding the role of Arfs in renal physiology, immunocytochemistry and Western blotting were performed to characterize the expression and targeting of Arf1 and Arf6 in epithelial cells in situ [3].
• In contrast, Arf6 was associated exclusively with basolateral membranes and vesicles in the CD [3].

Biological context of Arf6

• Arf6 regulates a clathrin-independent endocytic membrane recycling pathway in nonpolarized cells and clathrin-dependent endocytosis in polarized cells [4].
• 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 [5].

Anatomical context of Arf6

• A key effector for Arf6 is phosphatidylinositol 4-monophosphate 5-kinase, which catalyzes plasma membrane synthesis of phosphatidylinositol-4,5-bisphosphate (PIP2), a common required cofactor for several endocytic and exocytic membrane trafficking pathways [4].
• Long-term expression of a constitutively active Arf6 mutant in cells can lead to the depletion of PIP2 from the plasma membrane, its accumulation in intracellular vacuoles, and the inhibition of PIP2-dependent membrane trafficking at the plasma membrane [4].
• High glucose-induced membrane translocation of PKC betaI is associated with Arf6 in glomerular mesangial cells [6].
• However, phorbol ester (PMA) stimulation of cells cultured in high glucose significantly enhanced membrane association of PKC betaI and Arf6, but not Arf3 [6].
• Unlike other members of the ADP-ribosylation factor (ARF) family, Arf6 is localized to the plasma membrane and endosomes, and regulates membrane traffic from and into the plasma membrane [4].

Associations of Arf6 with chemical compounds

• Somatodendritic localization of the mRNA for EFA6A, a guanine nucleotide exchange protein for ARF6, in rat hippocampus and its involvement in dendritic formation [7].

Other interactions of Arf6

• MCs cultured in high glucose medium exhibited predominantly cytosolic localization of PKC betaI, Arf3 and Arf6 [6].
• The functional relationship between IPCEF1 and cytohesin 2 was assessed by studying the effect of IPCEF1 on the in vitro and in vivo stimulation of ADP-ribosylation factor 6 GTP formation by cytohesin 2 [8].
• Arf1 and Arf6 were associated with apical membranes and subapical vesicles in proximal tubules, where they colocalized with megalin [3].

References