ASSESSMENT OF NORMAL AND MUTANT HUMAN PRESENILIN FUNCTION IN CAENORHABDITIS ELEGANS

作者: D. Levitan , T. G. Doyle , D. Brousseau , M. K. Lee , G. Thinakaran

DOI: 10.1073/PNAS.93.25.14940

关键词: Caenorhabditis elegansAlzheimer's diseaseProteolysisPresenilinCell typeHelminth proteinMutantMolecular biologyMembrane proteinBiology

摘要: We provide evidence that normal human presenilins can substitute for Caenorhabditis elegans SEL-12 protein in functional assays vivo . In addition, six familial Alzheimer disease-linked mutant were tested and found to have reduced ability rescue the sel-12 phenotype, suggesting they lower than normal presenilin activity. A 1 deletion variant fails be proteolytically processed a SEL-12 lacks C terminus display considerable activity this assay, suggesting neither proteolysis nor is absolutely required function. also show that expressed most neural nonneural cell types all developmental stages. The of mutant as yet unknown gain-of-function properties may a contributing factor development disease.

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