title: The G-protein regulator AGS3 controls an early event during macroautophagy in human intestinal HT-29 cells.
abstract: AGS3 contains GoLoco or G-protein regulatory motifs in its COOH-terminal half that stabilize the GDP-bound conformation of the alpha-subunit of the trimeric Gi3 protein. The latter is part of a signaling pathway that controls the lysosomal-autophagic catabolism in human colon cancer HT-29 cells. In the present work we show that the mRNA encoding for AGS3 is expressed in human intestinal cell lines (Caco-2 and HT-29) whatever their state of differentiation. Together with the full-length form, minute amounts of the mRNA encoding a NH2-terminal truncated form of AGS3, previously characterized in cardiac tissues, were also detected. Both the endogenous form of AGS3 and a tagged expressed form have a localization compatible with a role in the Galphai3-dependent control of autophagy. Accordingly, expressing its non-Galphai3-interacting NH2-terminal domain or its Galphai3-interacting COOH-terminal domain reversed the stimulatory role of AGS3 on autophagy. On the basis of biochemical and morphometric analysis, we conclude that AGS3 is involved in an early event during the autophagic pathway probably prior to the formation of the autophagosome. These data demonstrate that AGS3 is a novel partner of the Galphai3 protein in the control of a major catabolic pathway.
authors.affiliation: INSERM U504, 16 avenue Paul-Vaillant-Couturier, 94807 Villejuif Cedex, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Pattingre
authors.forename: Luc
authors.initials: L
authors.lastname: De Vries
authors.forename: Chantal
authors.initials: C
authors.lastname: Bauvy
authors.forename: Isabelle
authors.initials: I
authors.lastname: Chantret
authors.forename: Françoise
authors.initials: F
authors.lastname: Cluzeaud
authors.forename: Eric
authors.initials: E
authors.lastname: Ogier-Denis
authors.forename: Alain
authors.initials: A
authors.lastname: Vandewalle
authors.forename: Patrice
authors.initials: P
authors.lastname: Codogno
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D015870:Gene Expression; D019073:HT29 Cells; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007422:Intestines / Q000166:cytology; D008565:Membrane Proteins / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology*; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; C498819:GNAI3 protein, human; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D020962:Heterotrimeric GTP-Binding Proteins