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Neurogenetics
Published in: neurogenetics 4/2004

01-12-2004 | Original Article

Alternative splicing in the N-terminus of Alzheimer’s presenilin 1

Authors: Wiep Scheper, Rob Zwart, Frank Baas

Published in: Neurogenetics | Issue 4/2004

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Abstract.

Presenilin 1 (PS1) is mutated in the majority of familial cases of Alzheimer disease (AD). Although it is clear that PS1 is involved in the processing of the amyloid precursor protein (APP), the exact function of PS1 is still elusive. Human presenilin 1 (PS1) is alternatively spliced, resulting in the presence or absence of a four-amino acid motif, VRSQ, in the PS1 N-terminus. In human tissues, both isoforms are expressed. Here we report that mouse and rat only express the longer PS1 isoform. The presence of this motif introduces a potential phosphorylation site for protein kinase C. Because the splice occurs in the region of PS1 that we have previously shown to bind to rabGDI, this might provide a regulatory mechanism for this interaction. Our data show that the –VRSQ isoform binds rabGDI, but the +VRSQ does not. Moreover, mutation of the putatively phosphorylated threonine in PS1 disrupts the binding to rabGDI, showing its importance for the interaction. To our knowledge this is the first study showing a functional difference between PS1 splice variants. The possible consequences for APP processing and the pathogenesis of AD are discussed.
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Metadata
Title
Alternative splicing in the N-terminus of Alzheimer’s presenilin 1
Authors
Wiep Scheper
Rob Zwart
Frank Baas
Publication date
01-12-2004
Publisher
Springer-Verlag
Published in
Neurogenetics / Issue 4/2004
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI
https://doi.org/10.1007/s10048-004-0195-y

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