A heterotrimeric Gi3-protein controls autophagic sequestration in the human colon cancer cell line HT-29

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 degradativ...

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Bibliographic Details
Published in:The Journal of biological chemistry 1995-01, Vol.270 (1), p.13-16
Main Authors: Ogier-Denis, E, Couvineau, A, Maoret, J J, Houri, J J, Bauvy, C, De Stefanis, D, Isidoro, C, Laburthe, M, Codogno, P
Format: Article
Language:English
Subjects:
Adenosine Diphosphate Ribose - metabolism
Autophagy
Colonic Neoplasms
GTP-Binding Proteins - physiology
Humans
Tumor Cells, Cultured
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Summary: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.
ISSN:0021-9258