Transport to cell surface of intestinal sucrase-isomaltase is blocked in the Golgi apparatus in a patient with congenital sucrase-isomaltase deficiency.

A case of congenital sucrase-isomaltase deficiency in man was investigated. An intestinal biopsy sample from a 5-year-old girl lacked sucrase but possessed low residual isomaltase activity. Immunoelectron microscopy with monoclonal antibodies to sucrase-isomaltase in biopsy samples from healthy subjects revealed that sucrase-isomaltase was confined predominantly to the microvillus membrane of enterocytes and there was minimal labeling of the Golgi apparatus. In the patient immunoreactive sucrase-isomaltase was found almost exclusively in about three trans-Golgi cisternae and associated vesicular structures, while no specific labeling was associated with the microvillus membrane. Immunoprecipitation experiments with iodinated mucosal homogenates and a mixture of four monoclonal antibodies to sucrase-isomaltase revealed absence of enzyme subunits in the patients but presence of a Mr 210,000 protein that was also expressed in normal control biopsy specimens. This protein presumably is the high-mannose precursor of sucrase-isomaltase. Additional proteins of Mr 160,000-200,000 found in the patient but not in normal subjects might correspond to the crossreacting material found in the Golgi apparatus of the patient. Overall, the findings suggest that in the patient sucrase-isomaltase is synthesized and transported to the Golgi apparatus, where further transport is interrupted. The data imply that signals in sucrase-isomaltase that mediate its transfer from the endoplasmic reticulum to the Golgi apparatus differ from those mediating its transport from the Golgi apparatus to the cell surface.