Differential expression of presenilin-alpha and -beta (PSalpha and PSbeta) in Xenopus laevis: embryonic phosphorylation of PSalpha.
Mutations in genes encoding the highly homologous proteins, presenilin-1 and -2 (PS1 and PS2), are linked to the development of early-onset Alzheimer's disease. On the other hand, presenilins are known to play a critical role(s) in cell fate decisions during embryonic development in Caenorhabditis elegans. The messenger RNAs (mRNAs) of amphibian presenilin homologues PSalpha and PSbeta are most abundantly synthesized in the brain and the ovary, but are differentially degraded upon oocyte maturation and at the midblastula transition (MBT), respectively. In this study, we examined the spatiotemporal distribution of PSalpha and PSbeta proteins and their post-translational modification. The results were essentially consistent with the mRNA data and revealed moreover that PSalpha was present exclusively as processed molecules in the early embryos, while PSbeta was present mainly as unprocessed molecules (90%). Furthermore, the C-terminal fragment (CTF) of PSalpha was phosphorylated upon oocyte maturation and dephosphorylated at MBT, while no phosphorylation of the PSbeta CTF was detectable. Human PS1 CTF exogenously injected was also phosphorylated in Xenopus oocytes induced to mature in vitro by progesterone treatment. Two phosphorylation loci were mapped at Thr(320) and Ser(334) in the hydrophilic loop region of PSalpha. Our results suggest that PS1 and PS2 may play different roles under physiological conditions despite their high structural similarity.
Watanabe
Yoshihisa
Y
Genomic Medical Sciences, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 602-8566, Kyoto, Japan.
Tsujimura
Atsushi
A
Tabira
Takeshi
T
Hashimoto-Gotoh
Tamotsu
T
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D053763:Presenilins; D011374:Progesterone / Q000494:pharmacology; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000235:genetics / Q000378:metabolism*
D008565:Membrane Proteins; D053763:Presenilins; D029867:Xenopus Proteins; C105126:presenilin-alpha protein, Xenopus; C105127:presenilin-beta, protein, Xenopus; D011374:Progesterone