title: Internalization of exogenous ADP-ribosylation factor 6 (Arf6) proteins into cells.
abstract: Endogenous Arf6 is a myristoylated protein mainly involved in endosomal membrane traffic and structural organization at the plasma membrane. It has been shown that Arf6 mediates cancer cell invasion and shedding of plasma membrane microvesicles derived from tumor cells. In this article, we determined that Arf6 proteins both in the GDP and GTPγS bound forms can enter cells when simply added in the cell culture medium without requiring the myristoyl group. The GTPγS bound can enter cells at a faster rate than the GDP-bound Arf6. Despite the role of the endogenous Arf6 in endocytosis and membrane trafficking, the internalization of exogenous Arf6 may involve non-endocytic processes. As protein therapeutics is becoming important in medicine, we examined the effect of the uptake of Arf6 proteins on cellular functions and determined that exogenous Arf6 inhibits proliferation, invasion, and migration of cells. Future studies of the internalization of Arf6 mutants will reveal key residues that play a role in the internalization of Arf6 and its interaction and possible structural conformations bound to the plasma membrane.
authors.affiliation: Department of Medicine, Texas A&M University Health Science Center College of Medicine and Scott & White Memorial Hospital, 702 SW H.K. Dogen Loop, Medical Research Building, Room 111, Temple, TX 76508, USA.
authors.forename: Syeda H
authors.initials: SH
authors.lastname: Afroze
authors.forename: M Nasir
authors.initials: MN
authors.lastname: Uddin
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Cao
authors.forename: Alexzander
authors.initials: A
authors.lastname: Asea
authors.forename: Dawit
authors.initials: D
authors.lastname: Gizachew
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004705:Endocytosis; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D011994:Recombinant Proteins / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000089982:ADP-Ribosylation Factor 6; D011994:Recombinant Proteins; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006493:Heparin; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human