You are here : Home > The lab > Gα12 and Gα13 in cystic fibrosis: Role in F508del-CFTR degradation and in the control of intercellular junctions

Sylvain Chauvet

Gα12 and Gα13 in cystic fibrosis: Role in F508del-CFTR degradation and in the control of intercellular junctions



Page Web française.
Published on 15 December 2011
​

Thesis presented December 15, 2011

Abstract:
F508del, the most frequent mutation found in cystic fibrosis (CF) population, impacts CFTR (Cystic Fibrosis Transmembrane conductance Regulator) trafficking and causes its rapid degradation at the endoplasmic compartment, resulting in a significant decrease in Cl- secretion at the apical membrane of epithelial cells. F508del has two main features, significant thickening of the bronchial mucus and a reduction in the integrity of the luminal barrier of the bronchial epithelium. These two phenomena are involved in the invasion and infection of lung tissue by pathogenic bacteria such as Pseudomonas aeruginosa, exacerbating the inflammation and lung destruction.
The objective of this study was to determine the role of two proteins member of the heterotrimeric G proteins family, Gα12 and Gα13, in the degradation of the F508del CFTR, and in the control of junctional complexes in the normal and CF bronchial epithelium.
Our results show for the first time that Gα12 and Gα13 are down expressed in CF. Gα12, but not Gα13, is involved in the control of F508del-CFTR degradation through its interaction with Calnexin and HSP90 chaperones. Unlike kidney epithelia cells, Gα12 promotes the formation and maintenance of cell junctions in the bronchial epithelium by affecting E-cadherin​ and ZO-1 stability. Altogether, our results set therefore Gα12 as a significant actor of the CF disease.

Keywords:
F508del-CFTR, cystic fibrosis, endoplasmic reticulum, heterotrimeric G proteins, Gα12, Gα13, chaperones, HSP90, Calnexin, cell junctions, E-cadherin, ZO-1

Download this thesis.