Presenilin-2 mutations modulate amplitude and kinetics of inositol 1,4,5-trisphosphate-mediated calcium signals

Malcolm A. Leissring, Ian Parker, Frank M. LaFerla

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

Mutations in the two presenilin genes (PS1, PS2) account for the majority of early-onset familial Alzheimer's disease (FAD) cases. Converging evidence from a variety of experimental systems, including fibroblasts from FAD patients and transgenic animals, indicates that PS1 mutations modulate intracellular calcium signaling pathways. Despite the potential relevance of these changes to the pathogenesis of FAD, a comparable effect for PS2 has not yet been demonstrated experimentally. We examined the effects of wild-type PS2, and both of the identified FAD mutations in PS2, on intracellular calcium signaling in Xenopus oocytes. Inositol 1,4,5-trisphosphate (IP3)- evoked calcium signals were significantly potentiated in cells expressing either of the PS2 mutations relative to wild-type PS2-expressing cells and controls. Decay rates of calcium signals were also significantly accelerated in mutant PS2-expressing cells in a manner dependent upon IP3 concentration. The finding that mutations in both PS1 and PS2 modulate intracellular calcium signaling suggests that these disturbances may represent a common pathogenic mechanism of presenilin-associated FAD.

Original languageEnglish (US)
Pages (from-to)32535-32538
Number of pages4
JournalJournal of Biological Chemistry
Volume274
Issue number46
DOIs
StatePublished - Nov 12 1999
Externally publishedYes

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Presenilin-2
Inositol 1,4,5-Trisphosphate
Alzheimer Disease
Calcium
Mutation
Kinetics
Calcium Signaling
Presenilins
Fibroblasts
Genetically Modified Animals
Xenopus
Animals
Genes
Oocytes
Cells

ASJC Scopus subject areas

  • Biochemistry

Cite this

Presenilin-2 mutations modulate amplitude and kinetics of inositol 1,4,5-trisphosphate-mediated calcium signals. / Leissring, Malcolm A.; Parker, Ian; LaFerla, Frank M.

In: Journal of Biological Chemistry, Vol. 274, No. 46, 12.11.1999, p. 32535-32538.

Research output: Contribution to journalArticle

Leissring, Malcolm A. ; Parker, Ian ; LaFerla, Frank M. / Presenilin-2 mutations modulate amplitude and kinetics of inositol 1,4,5-trisphosphate-mediated calcium signals. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 46. pp. 32535-32538.
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