Anomalous apical plasma membrane phenotype in CK8-deficient mice indicatesa novel role for intermediate filaments in the polarization of simple epithelia

Previous results from our laboratory have indicated a requirement for CK in termediate filaments (IF) for the organization of the apical domain in pola rized epithelial cells in culture. The results seemed to be challenged by t he phenotype of cytokeratin (CK) 8-deficient mice, which comprises only col orectal hyperplasia, female sterility and a weaker hepatocyte integrity. In this work localization with anti-CK antibodies indicated that many Ck8(-/- ) epithelia still form IF in CK8-deficient mice, perhaps because of the exp ression of the promiscuous CK7, In the small intestine, only villus enteroc ytes lacked Ifs. These cells appeared to lose syntaxin 3, and three apical membrane proteins (alkaline phosphatase, sucrase isomaltase and cystic fibr osis transmembrane conductance regulator) as they progressed along the vill us. At the distal third of the villi, gamma -tubulin was found scattered wi thin the cytoplasm of enterocytes, in contrast to its normal sub-apical loc alization, and the microtubules were disorganized. These results could not be attributed to increased numbers of apoptotic or necrotic cells. The only other cell type we found without Ifs in CK8 null mice, the hepatocyte, dis played increased basolateral levels of one apical marker (HA4), indicating a correlation between the lack of intermediate filaments and an apical doma in phenotype, These data suggest a novel function for intermediate filament s organizing the apical pole of simple polarized epithelial cells.