Differential expression of presenilin-α and -β (PSα and PSβ) in Xenopus laevis: embryonic phosphorylation of PSα

Abstract

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 PSα and PSβ 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 PSα and PSβ proteins and their post-translational modification. The results were essentially consistent with the mRNA data and revealed moreover that PSα was present exclusively as processed molecules in the early embryos, while PSβ was present mainly as unprocessed molecules (90%). Furthermore, the C-terminal fragment (CTF) of PSα was phosphorylated upon oocyte maturation and dephosphorylated at MBT, while no phosphorylation of the PSβ 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 PSα. Our results suggest that PS1 and PS2 may play different roles under physiological conditions despite their high structural similarity.