Subcellular mechanisms of presenilin-mediated enhancement of calcium signaling

M. A. Leissring, F. M. LaFerla, N. Callamaras, I. Parker

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Mutations in presenilin-1 (PS1), the leading cause of early-onset, autosomal-dominant familial Alzheimer's disease (FAD), enhance calcium signaling mediated by inositol 1,4,5-trisphosphate (IP3). To elucidate the subcellular mechanisms underlying this enhancement, we used high resolution line-scanning confocal microscopy to image elementary calcium release events ("puffs") in Xenopus oocytes expressing wild-type or mutant PS1. Here we report that mutant PS1-rendered puffs more sensitive to IP3 and increased both the magnitude and the rate of calcium release during each event. These effects were not attributable to quantitative changes in the levels of IP3 receptors or their distribution on the ER, but were instead associated with an abnormal elevation of ER calcium stores. Together, our results suggest that the effects of mutant PS1 on calcium signaling are manifested predominantly at the level of the regulation of calcium stores rather than via perturbations in the numbers or activity of IP3-activated calcium release channels.

Original languageEnglish (US)
Pages (from-to)469-478
Number of pages10
JournalNeurobiology of Disease
Volume8
Issue number3
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Presenilins
Presenilin-1
Calcium Signaling
Calcium
Inositol 1,4,5-Trisphosphate Receptors
Inositol 1,4,5-Trisphosphate
Xenopus
Confocal Microscopy
Oocytes
Alzheimer Disease
Mutation

Keywords

  • Alzheimer's disease
  • Calcium
  • Confocal microscopy
  • Endoplasmic reticulum
  • Phosphoinositide
  • Presenilin
  • Xenopus oocytes

ASJC Scopus subject areas

  • Neurology

Cite this

Subcellular mechanisms of presenilin-mediated enhancement of calcium signaling. / Leissring, M. A.; LaFerla, F. M.; Callamaras, N.; Parker, I.

In: Neurobiology of Disease, Vol. 8, No. 3, 2001, p. 469-478.

Research output: Contribution to journalArticle

Leissring, MA, LaFerla, FM, Callamaras, N & Parker, I 2001, 'Subcellular mechanisms of presenilin-mediated enhancement of calcium signaling', Neurobiology of Disease, vol. 8, no. 3, pp. 469-478. https://doi.org/10.1006/nbdi.2001.0382
Leissring, M. A. ; LaFerla, F. M. ; Callamaras, N. ; Parker, I. / Subcellular mechanisms of presenilin-mediated enhancement of calcium signaling. In: Neurobiology of Disease. 2001 ; Vol. 8, No. 3. pp. 469-478.
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