SUPPRESSION OF VILLIN EXPRESSION BY ANTISENSE RNA IMPAIRS BRUSH-BORDER ASSEMBLY IN POLARIZED EPITHELIAL INTESTINAL-CELLS

We have used an antisense RNA strategy to investigate the role of the actin-associated protein, villin, in the brush-border morphogenesis of human intestinal CaCO2 cells. Stable expression of a cDNA encoding an tisense villin RNA resulted in the permanent down-regulation of the en dogenous villin message and dramatically affected brush-border assembl y. Ultrastructural and immunolocalization studies revealed that epithe lial cell polarity was largely maintained However, in contrast to brus h-border markers such as dipeptidyl-peptidase IV, the apical localizat ion of sucrase-isomaltase was specifically impaired. Retransfection of the villin antisense-expressing cell line with a cDNA encoding a part ial sense villin RNA restored both brush-border assembly and sucrase-i somaltase apical expression. The suggestion that brush-border morphoge nesis may be important for the trafficking of certain proteins is disc ussed.