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Title

Presenilin-1 influences processing of the acetylcholinesterase membrane anchor PRiMA

AuthorsGarcía Ayllón, María Salud; Campanari, María Letizia; Montenegro, María-Fernanda; Cuchillo-Ibáñez, Inmaculada; Belbin, Olivia; Lleó, Alberto; Tsim, Karl; Vidal, Cecilio J.; Sáez-Valero, Javier
KeywordsAcetylcholinesterase
PRiMA
Presenilin 1
γ-Secretase
Alzheimer's disease
Issue Date6-Feb-2014
PublisherElsevier
CitationNeurobiology of Aging 35(7): 1526-1536 (2014)
AbstractPresenilin-1 (PS1) is the catalytic component of the γ-secretase complex. In this study, we explore if PS1 participates in the processing of the cholinergic acetylcholinesterase (AChE). The major AChE variant expressed in the brain is a tetramer (G4) bound to a proline-rich membrane anchor (PRiMA). Overexpression of the transmembrane PRiMA protein in Chinese hamster ovary cells expressing AChE and treated with the γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester have enabled us to study whether, through its γ-secretase activity, PS1 participates in the processing of PRiMA-linked AChE. γ-Secretase inhibition led to a notable increase in the level of PRiMA-linked AChE, suggesting that γ-secretase is involved in the cleavage of PRiMA. We demonstrate that cleavage of PRiMA by γ-secretase results in a C-terminal PRiMA fragment. Immunofluorescence labeling allowed us to identify this PRiMA fragment in the nucleus. Moreover, we have determined changes in the proportion of the raft-residing AChE-PRiMA in a PS1 conditional knockout mouse. Our results are of interest as both enzymes have therapeutic relevance for Alzheimer's disease. © 2014 Elsevier Inc.
Publisher version (URL)http://dx.doi.org/10.1016/j.neurobiolaging.2014.01.147
URIhttp://hdl.handle.net/10261/103460
DOI10.1016/j.neurobiolaging.2014.01.147
Identifiersdoi: 10.1016/j.neurobiolaging.2014.01.147
issn: 1558-1497
Appears in Collections:(IN) Artículos
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