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Vol. 18, Issue 6, 2313-2321, June 2007

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Cell Polarity Development and Protein Trafficking in Hepatocytes Lacking E-Cadherin/-Catenin–based Adherens Junctions

Delphine Théard^*, Magdalena Steiner^*, Dharamdajal Kalicharan, Dick Hoekstra^*, and Sven C.D. van IJzendoorn^*

*Section of Membrane Cell Biology and Section of Electron Microscopy, Department of Cell Biology, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, The Netherlands

Submitted November 28, 2006; Revised March 19, 2007; Accepted March 29, 2007
Monitoring Editor: Keith Mostov

Using a mutant hepatocyte cell line in which E-cadherin and -catenin are completely depleted from the cell surface, and, consequently, fail to form adherens junctions, we have investigated adherens junction requirement for apical–basolateral polarity development and polarized membrane trafficking. It is shown that these hepatocytes retain the capacity to form functional tight junctions, develop full apical–basolateral cell polarity, and assemble a subapical cortical F-actin network, although with a noted delay and a defect in subsequent apical lumen remodeling. Interestingly, whereas hepatocytes typically target the plasma membrane protein dipeptidyl peptidase IV first to the basolateral surface, followed by its transcytosis to the apical domain, hepatocytes lacking E-cadherin–based adherens junctions target dipeptidyl peptidase IV directly to the apical surface. Basolateral surface-directed transport of other proteins or lipids tested was not visibly affected in hepatocytes lacking E-cadherin–based adherens junctions. Together, our data show that E-cadherin/-catenin–based adherens junctions are dispensable for tight junction formation and apical lumen biogenesis but not for apical lumen remodeling. In addition, we suggest a possible requirement for E-cadherin/-catenin–based adherens junctions with regard to the indirect apical trafficking of specific proteins in hepatocytes.

Address correspondence to: Sven C.D. van IJzendoorn (s.c.d.van.ijzendoorn{at}med.umcg.nl)