摘要

Presenilins are one of two types of critical genetic factors in familial Alzheimer's disease, and they regulate various cellular functions such as intracellular Ca(2+) homeostasis, the endoplasmic reticulum (ER) stress response, apoptosis, and synaptic transmission. We utilized Drosophila presenilin (psis) mutants as a model for studying the role of this gene in regulating acetylcholinesterase activity (AChE) and synaptic plasticity. Several lines of biochemical evidence indicated that AChE activity in a functionally null psis mutant (psn(B3)) was significantly reduced. In addition, we also found that psn(B3) mutant neuromuscular junctions (NMjs) had smaller synaptic boutons and altered localization of Discs large, a synaptic scaffolding protein at the synaptic terminals compared to wild-type controls. These phenotypic defects were completely rescued in transgenic lines expressing the long form of wild-type Psn under an endogenous psn promoter cassette (PEPC-Psn(WT); psn(B3) lines). Taken together, these results indicate that Psn is important for regulating AChE activity, the size of synaptic boutons, and the localization of DLG at synaptic terminals.

  • 出版日期2010-12