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Title: Quantitation and localization of intracellular redox active metals by X-ray fluorescence microscopy in cortical neurons derived from APP and APLP2 knockout tissue

Journal Article · · Metallomics
DOI:https://doi.org/10.1039/C4MT00176A· OSTI ID:1214335
 [1];  [2];  [3];  [4];  [5];  [5];  [4];  [4];  [1];  [1]
  1. Univ. of Melbourne (Australia)
  2. Australian Nuclear Science and Technology Organisation (ANSTO), Melbourne, VIC (Australia). Australian Synchrotron; Commonwealth Scientific and Industrial Research Organization (CSIRO), Dickson ACT (Australia)
  3. Elettra Sincrotrone Trieste (Italy)
  4. Australian Nuclear Science and Technology Organisation (ANSTO), Melbourne, VIC
  5. Argonne National Lab. (ANL), Argonne, IL (United States)
+ Show Author Affiliations

The amyloid precursor protein (APP) gene family includes APP and the amyloid precursor-like proteins, APLP1 and APLP2. These proteins contain metal binding sites for copper, zinc and iron and are known to have physiological roles in modulating the metal homeostasis in brain cells. Here we report the application of X-ray fluorescence microscopy (XFM) to investigate the subcellular distribution patterns of the metal ions Cu, Zn, Fe, and Ca in individual neurons derived from APP and APLP2 knockout mice brains to further define their role in metal homeostasis. These studies add to the growing body of data that the APP family of proteins are metalloproteins that have shared as well as distinct effects on metals. As we continue to delineate the cellular effects of the APP family of proteins it is important to consider how metals are involved in their actions.

Research Organization:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1214335
Journal Information:
Metallomics, Vol. 6, Issue 10; ISSN 1756-5901
Publisher:
Royal Society of ChemistryCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 16 works
Citation information provided by
Web of Science

References (36)

Isolation and characterization of APLP2 encoding a homologue of the Alzheimer's associated amyloid β protein precursor journal September 1993
The APP family of proteins: similarities and differences journal March 2007
Mice with Combined Gene Knock-Outs Reveal Essential and Partially Redundant Functions of Amyloid Precursor Protein Family Members journal November 2000
Identification of the Alzheimer's disease amyloid precursor protein (APP) and its homologue APLP2 as essential modulators of glucose and insulin homeostasis and growth: APP and APLP2 modulate glucose and insulin homeostasis and growth in vivo journal February 2008
Iron-Export Ferroxidase Activity of β-Amyloid Precursor Protein Is Inhibited by Zinc in Alzheimer's Disease journal September 2010
Gene knockout of amyloid precursor protein and amyloid precursor-like protein-2 increases cellular copper levels in primary mouse cortical neurons and embryonic fibroblasts journal October 2004
Combined deletions of amyloid precursor protein and amyloid precursor-like protein 2 reveal different effects on mouse brain metal homeostasis journal January 2014
The βA4 amyloid precursor protein binding to copper journal July 1994
The Amyloid Precursor Protein of Alzheimer's Disease in the Reduction of Copper(II) to Copper(I) journal March 1996
Cysteine 144 Is a Key Residue in the Copper Reduction by the β-Amyloid Precursor Protein journal September 1999
Copper levels are increased in the cerebral cortex and liver of APP and APLP2 knockout mice journal September 1999
Structure of the Alzheimer's Disease Amyloid Precursor Protein Copper Binding Domain: A REGULATOR OF NEURONAL COPPER HOMEOSTASIS journal February 2003
Solution structure of the fourth metal-binding domain from the Menkes copper-transporting ATPase journal January 1998
Solution Structure of the Cu(I) and Apo Forms of the Yeast Metallochaperone, Atx1 † , ‡ journal February 2001
Overexpression of Alzheimer's Disease Amyloid-β Opposes the Age-dependent Elevations of Brain Copper and Iron journal September 2002
In vivo reduction of amyloid-  by a mutant copper transporter journal November 2003
Dietary Cu stabilizes brain superoxide dismutase 1 activity and reduces amyloid A  production in APP23 transgenic mice journal November 2003
β-amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity journal May 1995
Generation of APLP2 KO Mice and Early Postnatal Lethality in APLP2/APP Double KO Mice journal November 1997
Enhanced Toxicity and Cellular Binding of a Modified Amyloid β Peptide with a Methionine to Valine Substitution journal July 2004
Stereospecific interactions are necessary for Alzheimer disease amyloid-β toxicity journal February 2011
Chemical alterations to murine brain tissue induced by formalin fixation: implications for biospectroscopic imaging and mapping studies of disease pathogenesis journal January 2011
The X-ray Fluorescence Microscopy Beamline at the Australian Synchrotron conference January 2011
Quantitative PIXE trace element imaging of minerals using the new CSIRO–GEMOC Nuclear Microprobe journal April 2002
Protein length in eukaryotic and prokaryotic proteomes journal June 2005
The Sulfur-Containing Amino Acids: An Overview journal June 2006
Aging results in copper accumulations in glial fibrillary acidic protein-positive cells in the subventricular zone journal July 2013
Copper and Zinc Metallation Status of Copper-Zinc Superoxide Dismutase from Amyotrophic Lateral Sclerosis Transgenic Mice journal November 2010
β-Amyloid precursor protein localization in the Golgi apparatus in neuron and oligodendrocytes. An immunocytochemical structural and ultrastructural study in normal and axotomized neurons journal October 1992
Copper Promotes the Trafficking of the Amyloid Precursor Protein journal December 2010
X-ray fluorescence microscopy reveals large-scale relocalization and extracellular translocation of cellular copper during angiogenesis journal February 2007
Imaging of the intracellular topography of copper with a fluorescent sensor and by synchrotron x-ray fluorescence microscopy journal August 2005
Novel Zinc-binding Site in the E2 Domain Regulates Amyloid Precursor-like Protein 1 (APLP1) Oligomerization journal May 2014
Presynaptic and Postsynaptic Interaction of the Amyloid Precursor Protein Promotes Peripheral and Central Synaptogenesis journal September 2009
Mechanisms contributing to the deficits in hippocampal synaptic plasticity in mice lacking amyloid precursor protein journal March 1999
Increased asynchronous release and aberrant calcium channel activation in amyloid precursor protein deficient neuromuscular synapses journal November 2007

Cited By (2)

Quantitative Probing of Cu 2+ Ions Naturally Present in Single Living Cells journal March 2016
Cross talk between neurometals and amyloidogenic proteins at the synapse and the pathogenesis of neurodegenerative diseases journal January 2017

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