title: Quantitation and localization of intracellular redox active metals by X-ray fluorescence microscopy in cortical neurons derived from APP and APLP2 knockout tissue.
abstract: 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.
authors.affiliation: Department of Pathology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia. j.ciccotosto@unimelb.edu.au.
authors.forename: Giuseppe D
authors.initials: GD
authors.lastname: Ciccotosto
authors.forename: Simon A
authors.initials: SA
authors.lastname: James
authors.forename: Matteo
authors.initials: M
authors.lastname: Altissimo
authors.forename: David
authors.initials: D
authors.lastname: Paterson
authors.forename: Stefan
authors.initials: S
authors.lastname: Vogt
authors.forename: Barry
authors.initials: B
authors.lastname: Lai
authors.forename: Martin D
authors.initials: MD
authors.lastname: de Jonge
authors.forename: Daryl L
authors.initials: DL
authors.lastname: Howard
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Bush
authors.forename: Roberto
authors.initials: R
authors.lastname: Cappai
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D003300:Copper / Q000032:analysis / Q000378:metabolism; D055786:Gene Knockout Techniques; D005838:Genotype; D007501:Iron / Q000032:analysis; D008670:Metals / Q000032:analysis* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010084:Oxidation-Reduction; D014965:X-Rays; D015032:Zinc / Q000032:analysis / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; C492952:Aplp2 protein, mouse; D008670:Metals; D003300:Copper; D007501:Iron; D015032:Zinc; D002118:Calcium