Calnuc binds to Alzheimer's beta-amyloid precursor protein and affects its biogenesis.

Calnuc binds to Alzheimer's beta-amyloid precursor protein and affects its biogenesis. Research Abstract Details 

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Calnuc binds to Alzheimer's beta-amyloid precursor protein and affects its biogenesis. Abstract Text:

Ping Lin,Feng Li,Yun-Wu Zhang,Haining Huang,Gary Tong,Marilyn Gist Farquhar,Huaxi Xu,

Calnuc, a Golgi calcium binding protein, plays a key role in the constitution of calcium storage. Abnormal calcium homeostasis has been linked to Alzheimer's disease (AD). Excessive production and/or accumulation of beta-amyloid (Abeta) peptides that are proteolytically derived from the beta-amyloid precursor protein (APP) have been linked to the pathogenesis of AD. APP has also been indicated to play multiple physiological functions. In this study, we demonstrate that calnuc interacts with APP through direct binding to the carboxyl-terminal region of APP, possibly in a calcium-sensitive manner. Immunofluorescence study revealed that the two proteins co-localize in the Golgi in both cultured cells and mouse brains. Over-expression of calnuc in neuroblastoma cells significantly reduces the level of endogenous APP. Conversely, down-regulation of calnuc by siRNA increases cellular levels of APP. Additionally, we show that over-expression of calnuc down-regulates the APP mRNA level and inhibits APP biosynthesis, which in turn results in a parallel reduction of APP proteolytic metabolites, sAPP, CTFs and Abeta. Furthermore, we found that the level of calnuc was significantly decreased in the brain of AD patients as compared with that of age-matched non-AD controls. Our results suggest a novel function of calnuc in modulating the levels of APP and its proteolytic metabolites, which may further affect the patho/physiological functions of APP including AD pathogenesis.

Calnuc binds to Alzheimer's beta-amyloid precursor protein and affects its biogenesis. Publishing Authors By Initials

P Lin,F Li,YW Zhang,H Huang,G Tong,MG Farquhar,H Xu,

For similar investigative techniques: genetic techniques: cloning, molecular: two-hybrid system techniques research abstracts see: investigative techniques: genetic techniques: cloning, molecular: two-hybrid system techniques research

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Calnuc binds to Alzheimer's beta-amyloid precursor protein and affects its biogenesis. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of neurochemistry

VOLUME: 100

Page Numbers: 1505-14

Journal Abbreviation: J. Neurochem.

ISSN: 0022-3042

DAY: 3

MONTH: Mar

YEAR: 2007

Calnuc binds to Alzheimer's beta-amyloid precursor protein and affects its biogenesis. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985190

Calnuc binds to Alzheimer's beta-amyloid precursor protein and affects its biogenesis. Keywords Mesh Terms:

KEYWORDS: Two-Hybrid System Techniques

MESH TERMS: methods

Chemical & Substance for Abstract: Calnuc binds to Alzheimer's beta-amyloid precursor protein and affects its biogenesis. Information

Substance Name: Calcium

Registry Number: 7440-70-2

Grant and Affiliation Information for Calnuc binds to Alzheimer's beta-amyloid precursor protein and affects its biogenesis.

AFFILIATION: Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California 92037, USA.

Country: England

AGENCY: United States NINDS

GRANT: R01 NS046673

ACRONYM: NS

MEDLINETA: J Neurochem

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