THE CONSTITUTIVE EXOCYTOTIC PATHWAY IN MICROVILLOUS ATROPHY

Microvillous atrophy is a disorder within the intractable diarrhea of infancy syndrome. The disease is believed to stem from a transport def ect that prevents exocytosis of brush border-related material. We inve stigated this hypothesis by examining the direct constitutive exocytot ic pathway using sucrase-isomaltase as a representative protein. We al so studied various other brush border and lysosomal marker enzymes. Th e biosynthesis and localization of selected intestinal epithelial enzy mes were studied in small-intestinal mucosal biopsy specimens from a t otal of nine children with microvillous atrophy by: (a) metabolic labe ling in organ culture, (b) radioiodination and immunoprecipitation, (c ) indirect immunoperoxidase immunocytochemistry, and (d) immunogold el ectron microscopy. The results demonstrated that brush border enzymes were synthesized normally and could be located in the apical brush bor der membrane and on microvillous membrane within microvillous inclusio ns. Brush border enzymes were not detected in the ''secretory granules '' that accumulated within the apical cytoplasm of epithelial cells. L ysosomal enzymes were only detected within lysosomal bodies. Thus, the direct constitutive pathway is not involved in microvillous atrophy, and a disturbance of endocytosis or the indirect constitutive pathway is unlikely. Any transport defect in the disease probably involves a d ifferent, unidentified exocytotic pathway.