Expression profiles of two human APH-1 genes and their roles in formation of presenilin complexes.
APH-1 is a polytopic membrane protein that functions as a component of presenilin-gamma-secretase complexes. Two homologous genes of APH-1 exist in humans, APH-1a and APH-1b, and alternative splicing of the former generates two isoforms, APH-1aS and APH-1aL. We performed semi-quantitative reverse transcription-PCR analysis to investigate mRNA expression of these three APH-1 forms in human cell lines and tissues. We found that both APH-1a and APH-1b were expressed in almost all tissues, and that APH-1aS was 1.5-3 times more abundantly expressed than APH-1aL. We examined the effect of small interfering RNA-mediated knock down of APH-1a or APH-1b on APH-1 mRNA expression and presenilin complex protein expression. We found that knock down of APH-1a, but not APH-1b, resulted in impaired maturation of nicastrin and reduced expression of presenilin 1, presenilin 2, and PEN-2 proteins. These findings indicate that APH-1a plays an essential role in the formation of presenilin-gamma-secretase complexes.
Saito
Shinya
S
Department of Demyelinating Disease and Aging, National Institute of Neuroscience, NCNP, Kodaira, Tokyo 187-8502, Japan.
Araki
Wataru
W
D002460:Cell Line; D010450:Endopeptidases; D020869:Gene Expression Profiling; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D010447:Peptide Hydrolases; D053764:Presenilin-1; D053766:Presenilin-2; D011485:Protein Binding; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D008565:Membrane Proteins; D046912:Multiprotein Complexes; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; D012333:RNA, Messenger; C475154:APH1A protein, human; C475155:APH1B protein, human; D010450:Endopeptidases; D010447:Peptide Hydrolases