A role for presenilin in post‐stress regulation: effects of presenilin mutations on Ca2+currents inDrosophila
| Autor: | Yalin Wang, Yubing Lv, Yu Hong, Zuoping Xie, Yi Zhong, Yisheng Lu, Yihong Ye, Mark E. Fortini |
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| Rok vydání: | 2007 |
| Předmět: |
Heterozygote
Patch-Clamp Techniques Period (gene) Restriction Mapping Neuromuscular Junction Biology Polymerase Chain Reaction Biochemistry Presenilin Neuromuscular junction Synapse Alzheimer Disease mental disorders Genetics medicine Animals Drosophila Proteins Humans Calcium Signaling Cloning Molecular Molecular Biology Calcium signaling Neuronal Plasticity Endoplasmic reticulum Homozygote Presenilins Anatomy Recombinant Proteins Cell biology medicine.anatomical_structure nervous system Larva Synaptic plasticity Unfolded protein response Drosophila Biotechnology |
| Zdroj: | The FASEB Journal. 21:2368-2378 |
| ISSN: | 1530-6860 0892-6638 |
| Popis: | It has been shown that presenilin is involved in maintaining Ca2+ homeostasis in neurons, including regulating endoplasmic reticulum (ER) Ca2+ storage. From studies of primary cultures and cell lines, however, its role in stress-induced responses is still controversial. In the present study we analyzed the effects of presenilin mutations on membrane currents and synaptic functions in response to stress using an in vivo preparation. We examined voltage-gated K+ and Ca2+ currents at the Drosophila larval neuromuscular junction (NMJ) with voltage-clamp recordings. Our data showed that both currents were generally unaffected by loss-of-function or Alzheimer's disease (AD) -associated presenilin mutations under normal or stress conditions induced by heat shock (HS) or ER stress. In larvae expressing the mutant presenilins, prolonged Ca2+ tail current, reflecting slower deactivation kinetics of Ca2+ channels, was observed 1 day after stress treatments were terminated. It was further demonstrated that the L-type Ca2+ channel was specifically affected under these conditions. Moreover, synaptic plasticity at the NMJ was reduced in larvae expressing the mutant presenilins. At the behavioral level, memory in adult flies was impaired in the presenilin mutants 1 day after HS. The results show that presenilin function is important during the poststress period and its impairment contributes to memory dysfunction observed during adaptation to normal conditions after stress. Our findings suggest a new stress-related mechanism by which presenilin may be implicated in the neuropathology of AD. |
| Databáze: | OpenAIRE |
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