Rab6 membrane association is dependent of Presenilin 1 and cellular phosphorylation events

W. Scheper; R. Zwart; F. Baas

doi:10.1016/j.molbrainres.2003.11.013

Rab6 membrane association is dependent of Presenilin 1 and cellular phosphorylation events

W. Scheper, R. Zwart, F. Baas

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Abstract

Processing of the amyloid precursor protein (APP) by α-secretase precludes the formation of β-amyloid (Aβ). Therefore, the increase of cleavage by α-secretase upon stimulation by protein kinase C (PKC) is of potential therapeutic interest for Alzheimer's disease (AD). Unknown is whether phosphorylation by PKC increases α-secretase-mediated cleavage directly or indirectly, for example, by modulation of APP trafficking. Because modulation of Rab6-mediated transport has been shown to affect APP processing, we investigated the regulation of Rab6 membrane association by PKC and its relation to PS1. We show that in fibroblasts, Rab6 membrane association is PKC dependent, an effect strongly potentiated by inhibition of calcineurin. Moreover, we demonstrate that this regulation of Rab6 membrane association is dependent on PS1. The possible implications for APP processing and AD are discussed. © 2004 Elsevier B.V. All rights reserved.

Original language	English
Pages (from-to)	17-23
Journal	Molecular Brain Research
Volume	122
Issue number	1
DOIs	https://doi.org/10.1016/j.molbrainres.2003.11.013
Publication status	Published - 17 Mar 2004
Externally published	Yes

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title = "Rab6 membrane association is dependent of Presenilin 1 and cellular phosphorylation events",

abstract = "Processing of the amyloid precursor protein (APP) by α-secretase precludes the formation of β-amyloid (Aβ). Therefore, the increase of cleavage by α-secretase upon stimulation by protein kinase C (PKC) is of potential therapeutic interest for Alzheimer's disease (AD). Unknown is whether phosphorylation by PKC increases α-secretase-mediated cleavage directly or indirectly, for example, by modulation of APP trafficking. Because modulation of Rab6-mediated transport has been shown to affect APP processing, we investigated the regulation of Rab6 membrane association by PKC and its relation to PS1. We show that in fibroblasts, Rab6 membrane association is PKC dependent, an effect strongly potentiated by inhibition of calcineurin. Moreover, we demonstrate that this regulation of Rab6 membrane association is dependent on PS1. The possible implications for APP processing and AD are discussed. {\textcopyright} 2004 Elsevier B.V. All rights reserved.",

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T1 - Rab6 membrane association is dependent of Presenilin 1 and cellular phosphorylation events

AU - Scheper, W.

AU - Zwart, R.

AU - Baas, F.

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Y1 - 2004/3/17

N2 - Processing of the amyloid precursor protein (APP) by α-secretase precludes the formation of β-amyloid (Aβ). Therefore, the increase of cleavage by α-secretase upon stimulation by protein kinase C (PKC) is of potential therapeutic interest for Alzheimer's disease (AD). Unknown is whether phosphorylation by PKC increases α-secretase-mediated cleavage directly or indirectly, for example, by modulation of APP trafficking. Because modulation of Rab6-mediated transport has been shown to affect APP processing, we investigated the regulation of Rab6 membrane association by PKC and its relation to PS1. We show that in fibroblasts, Rab6 membrane association is PKC dependent, an effect strongly potentiated by inhibition of calcineurin. Moreover, we demonstrate that this regulation of Rab6 membrane association is dependent on PS1. The possible implications for APP processing and AD are discussed. © 2004 Elsevier B.V. All rights reserved.

AB - Processing of the amyloid precursor protein (APP) by α-secretase precludes the formation of β-amyloid (Aβ). Therefore, the increase of cleavage by α-secretase upon stimulation by protein kinase C (PKC) is of potential therapeutic interest for Alzheimer's disease (AD). Unknown is whether phosphorylation by PKC increases α-secretase-mediated cleavage directly or indirectly, for example, by modulation of APP trafficking. Because modulation of Rab6-mediated transport has been shown to affect APP processing, we investigated the regulation of Rab6 membrane association by PKC and its relation to PS1. We show that in fibroblasts, Rab6 membrane association is PKC dependent, an effect strongly potentiated by inhibition of calcineurin. Moreover, we demonstrate that this regulation of Rab6 membrane association is dependent on PS1. The possible implications for APP processing and AD are discussed. © 2004 Elsevier B.V. All rights reserved.

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DO - 10.1016/j.molbrainres.2003.11.013

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SN - 0169-328X

VL - 122

SP - 17

EP - 23

JO - Molecular Brain Research

JF - Molecular Brain Research

IS - 1

ER -

Rab6 membrane association is dependent of Presenilin 1 and cellular phosphorylation events

Abstract

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