Altered folding, turnover, and polarized sorting act in concert to define a novel pathomechanism of XXXX .

@entity1 @entity70850 @entity462 @entity23125 @entity535 @entity74 @entity369
Naturally occurring mutants of membrane and secretory proteins are often associated with the pathogenesis of @entity1 diseases. Here, we describe the molecular basis of a novel phenotype of @entity23125 ( @entity23125 ), a @entity74 of the @entity1 intestine in which several structural features and functional capacities of the brush-border enzyme complex sucrase-isomaltase (SI) are affected. The cDNA encoding SI from a @entity1 with @entity23125 reveals a mutation in the isomaltase subunit of SI that results in the substitution of a @entity462 by an @entity369 at @entity535 residue 635 ( @entity70850 ). When this mutation is introduced into the wild type cDNA of SI a mutant enzyme, SI( @entity70850 ), is generated that shows a predominant localization in the endoplasmic reticulum. Nevertheless, a definite localization of SI( @entity70850 ) in the Golgi apparatus and at the cell surface could be also observed. Epitope mapping with conformation-specific mAbs protease sensitivity assays, and enzymatic activity measurements demonstrate an altered folding pattern of SI( @entity70850 ) that is responsible for a substantially increased turnover rate and an aberrant sorting profile. Thus, SI( @entity70850 ) becomes distributed also at the basolateral membrane in contrast to wild type SI. Concomitant with the altered sorting pattern, the partial detergent extractability of wild type SI shifts to a complete detergent solubility with Triton X-100. The mutation has therefore affected an epitope responsible for the apical targeting fidelity of SI. Altogether, the combined effects of the @entity70850 mutation on the turnover rate, function, polarized sorting, and detergent solubility of SI constitute a unique and novel pathomechanism of @entity23125 .
