Cloning and characterization of the Drosophila presenilin homologue.
Mutations in two genes, PS1 and PS2, coding for the presenilins, have been linked to the early onset form of familial Alzheimer's disease (AD). Here we report the identification of a Drosophila melanogaster homologue of human PS genes, Dps, which maps to band 77B-C on chromosome 3 and is expressed at multiple developmental stages. The predicted amino acid sequence of the Dps product is 53% identical to human presenilins, with the greatest similarity in the putative transmembrane domains, the hydrophobic domains at the beginning and the end of the cytoplasmic TM6-TM7 loop and the C-terminus. Analysis of Dps in a genetically tractable model system such as Drosophila may provide insight into the mechanisms of Alzheimer's disease (AD) necessary for the development of rational therapeutic approaches.
Boulianne
G L
GL
Hospital for Sick Children, Department of Physiology and Zoology, University of Toronto, Ontario, Canada.
Livne-Bar
I
I
Humphreys
J M
JM
Liang
Y
Y
Lin
C
C
Rogaev
E
E
St George-Hyslop
P
P
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002462:Cell Membrane / Q000502:physiology; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology*; D004625:Embryo, Nonmammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D009865:Oocytes / Q000502:physiology; D016133:Polymerase Chain Reaction; D053764:Presenilin-1; D053766:Presenilin-2; D053763:Presenilins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D029721:Drosophila Proteins; D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; D053763:Presenilins; C106427:Psn protein, Drosophila