This Article Full Text (PDF) Other Versions of this Article: MCB.02065-07v1 28/9/2908    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Silveyra, M.-X. Articles by Sáez-Valero, J. Search for Related Content PubMed PubMed Citation Articles by Silveyra, M.-X. Articles by Sáez-Valero, J.

 Previous Article  |  Next Article 

Mol. Cell. Biol. doi:10.1128/MCB.02065-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Presenilin-1 interacts with acetylcholinesterase and alters its enzymatic activity and glycosylation

Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Sant Joan d'Alacant, E-03550; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain; Department of Pathology, The University of Melbourne, VIC 3010, and The Mental Health Research Institute of Victoria, Parkville, VIC 3052, and The Centre for Neuroscience, The University of Melbourne, VIC 3010 Australia; Departamento de Bioquímica y Biología Molecular-A, Universidad de Murcia, E-30071 Spain

^* To whom correspondence should be addressed. Email: j.saez{at}umh.es.

	Abstract

Presenilin 1 (PS1) plays a critical role in the -secretase processing of the amyloid precursor protein to generate the -amyloid peptide, which accumulates in plaques in the pathogenesis of Alzheimer's disease (AD). Mutations in PS1 cause early onset AD and proteins that interact with PS1 are of major functional importance. We report co-immunoprecipitation of PS1 and acetylcholinesterase (AChE), an enzyme associated with amyloid plaques. Binding occurs through PS1 N-terminal fragment independent of the peripheral binding site of AChE. Subcellular co-localization of PS1 and AChE in cultured cells and co-expression patterns of PS1 and AChE in brain sections from controls and subjects with sporadic or familial AD, indicated PS1 and AChE are located in the same intracellular compartments, including perinuclear compartments. PS1-A246E pathogenic mutation expressed in transgenic mice, leads to decreased AChE activity and alteration of AChE glycosylation and peripheral binding site, which may reflect a shift in protein conformation and disturbed AChE maturation. In both, the transgenic mice and humans, mutant PS1 impairs co-immunoprecipitation with AChE. The results indicate that PS1 can interact with AChE and influence its expression, supporting the notion of cholinergic-amyloid interrelationships.