title: A heterotrimeric Gi3-protein controls autophagic sequestration in the human colon cancer cell line HT-29.
abstract: Human colon cancer HT-29 cells exhibit a differentiation-dependent autophagic-lysosomal pathway that is responsible for the degradation of a pool of newly synthesized N-linked glycoproteins in undifferentiated cells. In the present study, we have investigated the molecular control of this degradative pathway in undifferentiated HT-29 cells. For this purpose, we have modulated the function and expression of the heterotrimeric G-proteins (Gs and Gi) in these cells. After pertussis toxin treatment which ADP-ribosylates heterotrimeric Gi-proteins, we observed an inhibition of autophagic sequestration and the complete restoration of the passage of N-linked glycoproteins through the Golgi complex. In contrast, autophagic sequestration was not reduced by cholera toxin, which acts on heterotrimeric Gs-proteins. Further insights on the nature of the pertussis toxin-sensitive alpha subunit controlling autophagic sequestration were obtained by cDNA transfections of alpha i subunits. Overexpression of the alpha i3 subunit increased autophagic sequestration and degradation in undifferentiated cells, whereas overexpression of the alpha i2 subunit, the only other pertussis toxin-sensitive alpha subunit expressed in HT-29 cells, did not alter the rate of autophagy.
authors: INSERM U410, Faculté de Médecine Xavier Bichat, Paris, France.
authors: E
authors: E
authors: Ogier-Denis
authors: A
authors: A
authors: Couvineau
authors: J J
authors: JJ
authors: Maoret
authors: J J
authors: JJ
authors: Houri
authors: C
authors: C
authors: Bauvy
authors: D
authors: D
authors: De Stefanis
authors: C
authors: C
authors: Isidoro
authors: M
authors: M
authors: Laburthe
authors: P
authors: P
authors: Codogno
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D001343:Autophagy; D003110:Colonic Neoplasms; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D014407:Tumor Cells, Cultured
chemical_list: D000246:Adenosine Diphosphate Ribose; D019204:GTP-Binding Proteins