A role for presenilin in post-stress regulation

Effects of presenilin mutations on Ca2+ currents in Drosophila

Yisheng Lu, Yubing Lv, Yihong Ye, Yalin Wang, Yu Hong, Mark E. Fortini, Yi Zhong, Zuoping Xie

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

It has been shown that presenilin is involved in maintaining Ca 2+ 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 Ca 2+ 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.

Original languageEnglish (US)
Pages (from-to)2368-2378
Number of pages11
JournalFASEB Journal
Volume21
Issue number10
DOIs
StatePublished - Aug 1 2007

Fingerprint

Presenilins
Drosophila
Mutation
Neuromuscular Junction
Larva
Shock
Alzheimer Disease
Hot Temperature
Presenilin-1
Synaptic Membranes
Endoplasmic Reticulum Stress
Neuronal Plasticity
Data storage equipment
Clamping devices
Diptera
Endoplasmic Reticulum
Electric potential
Tail
Cell culture
Homeostasis

Keywords

  • Alzheimer's disease
  • Heat shock
  • L-type Ca channel
  • Synaptic function

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

A role for presenilin in post-stress regulation : Effects of presenilin mutations on Ca2+ currents in Drosophila. / Lu, Yisheng; Lv, Yubing; Ye, Yihong; Wang, Yalin; Hong, Yu; Fortini, Mark E.; Zhong, Yi; Xie, Zuoping.

In: FASEB Journal, Vol. 21, No. 10, 01.08.2007, p. 2368-2378.

Research output: Contribution to journalArticle

Lu, Y, Lv, Y, Ye, Y, Wang, Y, Hong, Y, Fortini, ME, Zhong, Y & Xie, Z 2007, 'A role for presenilin in post-stress regulation: Effects of presenilin mutations on Ca2+ currents in Drosophila', FASEB Journal, vol. 21, no. 10, pp. 2368-2378. https://doi.org/10.1096/fj.06-6380com
Lu, Yisheng ; Lv, Yubing ; Ye, Yihong ; Wang, Yalin ; Hong, Yu ; Fortini, Mark E. ; Zhong, Yi ; Xie, Zuoping. / A role for presenilin in post-stress regulation : Effects of presenilin mutations on Ca2+ currents in Drosophila. In: FASEB Journal. 2007 ; Vol. 21, No. 10. pp. 2368-2378.
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