Identification and characterization of a novel human APH-1b splice variant lacking exon 4.
APH-1 is one of the four essential components of the presenilin-gamma-secretase complex and has two human homologs, APH-1a, and APH-1b, both of which are seven-pass membrane proteins. Here, we identified a novel splice variant of human APH-1b. This variant lacks exon 4, which encodes the entire fourth transmembrane domain. The mRNA expression of this variant was detected in most tissues at low levels. In transiently transfected cells, protein expression of the APH-1b variant was much lower than that of the wild-type. Furthermore, exogenous expression of the APH-1-interacting protein, nicastrin, significantly increased the variant protein levels. These data suggest that the APH-1b variant protein is destabilized, and implies that the fourth transmembrane domain plays an important role in the protein stability and function of APH-1.
Saito
Shinya
S
Department of Demyelinating Disease and Aging, National Institute of Neuroscience, NCNP, Kodaira, Tokyo 187-8502, Japan.
Takahashi-Sasaki
Noriko
N
Araki
Wataru
W
D017398:Alternative Splicing; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D010450:Endopeptidases; D005091:Exons; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010447:Peptide Hydrolases; D012333:RNA, Messenger / Q000235:genetics*
D008565:Membrane Proteins; D012333:RNA, Messenger; C475155:APH1B protein, human; D010450:Endopeptidases; D010447:Peptide Hydrolases