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Expression of a Wild-type CFTR Maintains the Integrity of the Biosynthetic/Secretory Pathway in Human Cystic Fibrosis Pancreatic Duct Cells

Etienne Hollande¹, Christel Salvador-Cartier¹, Laetitia Alvarez and Marjorie Fanjul

Laboratoire de Biologie Cellulaire et Moléculaire des Epithéliums, Université Paul Sabatier, France (EH,CS-C,LA,MF), and INSERM U531, Institut Louis Bugnard (IFR 31) CHU Rangueil, Toulouse Cedex, France (EH,MF)

Correspondence to: Prof. E. Hollande, Laboratoire de Biologie Cellulaire et Moléculaire des Epithéliums, Université Paul Sabatier, 38, rue des 36 Ponts, 31400 Toulouse, France. E-mail: hollande{at}cict.fr

The structural integrity of the Golgi complex is essential to its functions in the maturation, sorting, and transport of plasma membrane proteins. Previously, we demonstrated that in pancreatic duct CFPAC-1 cells, which express F508 CFTR (cystic fibrosis transmembrane conductance regulator), the intracellular trafficking of carbonic anhydrase IV (CA IV), a membrane protein involved in HCO₃^– secretion, was impaired. To determine whether these abnormalities were related to changes in the Golgi complex, we examined the ultrastructure and distribution of Golgi compartments with regard to the microtubule cytoskeleton in CFPAC-1 cells transfected or not with the wild-type CFTR. Ultrastructural and immunocytochemical analysis showed that in polarized CFPAC-1 cells, Golgi stacks were disconnected from one another and scattered throughout the cytoplasm. The colocalization of CA IV with markers of Golgi compartments indicated the ability of stacks to transfer this enzyme. This Golgi dispersal was associated with abnormal microtubule distribution and multiplicity of the microtubule-organizing centers (MTOCs). In reverted cells, the normalization of Golgi structure, microtubule distribution, and MTOC number was observed. These observations suggest that the entire biosynthetic/secretory pathway is disrupted in CFPAC-1 cells, which might explain the abnormal intracellular transport of CA IV. Taken together, these results point to the fact that the expression of F508 CFTR affects the integrity of the secretory pathway. (J Histochem Cytochem 53:1539–1552, 2005)

Key Words: cystic fibrosis • Golgi complex • microtubules • protein trafficking • carbonic anhydrase IV • HCO₃^– secretion • pancreas • human

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