A role for presenilin in post-stress regulation: effects of presenilin mutations on Ca2+ currents in Drosophila

Lu, Y., Lv, Y., Ye, Y., Wang, Y., Hong, Y., Fortini, M. E., Zhong, Y., Xie, Z. (2007) A role for presenilin in post-stress regulation: effects of presenilin mutations on Ca2+ currents in Drosophila. Faseb Journal, 21 (10). pp. 2368-2378. ISSN 1530-6860 (Electronic)

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URL: http://www.fasebj.org/cgi/content/full/21/10/2368
DOI: 10.1096/fj.06-6380com

Abstract

It has been shown that presenilin is involved in maintaining Ca(2+) homeostasis in neurons, including regulating (ER) Ca(2+) 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 Ca(2+) 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 Ca(2+) 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 Ca(2+) 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.--Lu, Y., Lv, Y., Ye, Y., Wang, Y., Hong, Y., Fortini, M. E., Zhong, Y., Xie, Z. A role for presenilin in post-stress regulation: effects of presenilin mutations on Ca(2+) currents in Drosophila.

Item Type: Paper
Uncontrolled Keywords: L-type Ca2+ channel heat shock Alzheimer's disease synaptic function
Subjects: diseases & disorders > mental disorders > delirium dementia cognitive disorders > Alzheimer's disease
organism description > animal > insect > Drosophila
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > presenilin
organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > synapse
CSHL Authors:
Depositing User: CSHL Librarian
Date Deposited: 11 Nov 2011 15:31
Last Modified: 29 Nov 2011 20:07
URI: http://repository.cshl.edu/id/eprint/23085

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