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Article

Zinc Transporter-3 Knockout Mice Demonstrate Age-Dependent Alterations in the Metalloproteome

by
Sara M. Hancock
1,†,
Stuart D. Portbury
1,2,†,
Adam P. Gunn
1,‡,
Blaine R. Roberts
1,§,
Ashley I. Bush
1,2 and
Paul A. Adlard
1,2,*
1
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC 3010, Australia
2
The Melbourne Dementia Research Centre, Parkville, VIC 3052, Australia
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
‡
Current address: Institute for Applied Ecology, Faculty of Science and Technology, University of Canberra, Canberra, ACT 2601, Australia.
§
Current address: Department of Biochemistry, Emory School of Medicine, 4113 Rollins Research Building, Atlanta, GA 30322, USA.
Int. J. Mol. Sci. 2020, 21(3), 839; https://doi.org/10.3390/ijms21030839
Submission received: 9 December 2019 / Revised: 21 January 2020 / Accepted: 25 January 2020 / Published: 28 January 2020
(This article belongs to the Special Issue Zinc Biology 2019)
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Abstract

Metals are critical cellular elements that are involved in a variety of cellular processes, with recent literature demonstrating that zinc, and the synaptic zinc transporter (ZnT3), are specifically involved in learning and memory and may also be key players in age-related neurodegenerative disorders such as Alzheimer’s disease. Whilst the cellular content and location of metals is critical, recent data has demonstrated that the metalation state of proteins is a determinant of protein function and potential toxicity. As we have previously reported that ZnT3 knockout (KO) mice have deficits in total zinc levels at both 3 and 6 months of age, we were interested in whether there might be changes in the metalloproteomic profile in these animals. To do this, we utilised size exclusion chromatography-inductively coupled plasma mass spectrometry (SEC-ICP-MS) and examined hippocampal homogenates from ZnT3 KO and age-matched wild-type mice at 3, 6 and 18 months of age. Our data suggest that there are alterations in specific metal binding proteins, for zinc, copper and iron all being modulated in the ZnT3 KO mice compared to wild-type (WT). These data suggest that ZnT3 KO mice may have impairments in the levels or localisation of multiple transition metals, and that copper- and iron-dependent cellular pathways may also be impacted in these mice.
Keywords: Zinc; ZnT3; Alzheimer’s disease; metals; ageing Zinc; ZnT3; Alzheimer’s disease; metals; ageing

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MDPI and ACS Style

Hancock, S.M.; Portbury, S.D.; Gunn, A.P.; Roberts, B.R.; Bush, A.I.; Adlard, P.A. Zinc Transporter-3 Knockout Mice Demonstrate Age-Dependent Alterations in the Metalloproteome. Int. J. Mol. Sci. 2020, 21, 839. https://doi.org/10.3390/ijms21030839

AMA Style

Hancock SM, Portbury SD, Gunn AP, Roberts BR, Bush AI, Adlard PA. Zinc Transporter-3 Knockout Mice Demonstrate Age-Dependent Alterations in the Metalloproteome. International Journal of Molecular Sciences. 2020; 21(3):839. https://doi.org/10.3390/ijms21030839

Chicago/Turabian Style

Hancock, Sara M., Stuart D. Portbury, Adam P. Gunn, Blaine R. Roberts, Ashley I. Bush, and Paul A. Adlard. 2020. "Zinc Transporter-3 Knockout Mice Demonstrate Age-Dependent Alterations in the Metalloproteome" International Journal of Molecular Sciences 21, no. 3: 839. https://doi.org/10.3390/ijms21030839

APA Style

Hancock, S. M., Portbury, S. D., Gunn, A. P., Roberts, B. R., Bush, A. I., & Adlard, P. A. (2020). Zinc Transporter-3 Knockout Mice Demonstrate Age-Dependent Alterations in the Metalloproteome. International Journal of Molecular Sciences, 21(3), 839. https://doi.org/10.3390/ijms21030839

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