title: ADP-ribosylation factor 6 regulation of phosphatidylinositol-4,5-bisphosphate synthesis, endocytosis, and exocytosis.
abstract: 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. Arf6 regulates a clathrin-independent endocytic membrane recycling pathway in nonpolarized cells and clathrin-dependent endocytosis in polarized cells. It also regulates recycling endosome traffic back to the plasma membrane as well as dense-core vesicle exocytosis in neuroendocrine cells. 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. 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.
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences at Kagawa, Tokushima-bunri University, Japan.
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Aikawa
authors.forename: Thomas F J
authors.initials: TF
authors.lastname: Martin
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects*; D005089:Exocytosis / Q000187:drug effects*; D007150:Immunohistochemistry; D016716:PC12 Cells; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000096:biosynthesis*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051381:Rats
chemical_list: D000089982:ADP-Ribosylation Factor 6; D019269:Phosphatidylinositol 4,5-Diphosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase; D020727:ADP-Ribosylation Factors; C000715349:Arf6 protein, rat