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Systematic proteomic analysis identifies beta-site amyloid precursor protein cleaving enzyme 2 and 1 (BACE2 and BACE1) substrates in pancreatic beta-cells

Stützer, Ina and Selevsek, Nathalie and Esterhazy, Daria and Schmidt, Alexander and Aebersold, Ruedi and Stoffel, Markus. (2013) Systematic proteomic analysis identifies beta-site amyloid precursor protein cleaving enzyme 2 and 1 (BACE2 and BACE1) substrates in pancreatic beta-cells. Journal of biological chemistry, Vol. 288, H. 15. pp. 10536-10547.

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Official URL: http://edoc.unibas.ch/dok/A6094003

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Abstract

Expansion of functional islet β-cell mass is a physiological process to compensate for increased insulin demand. Deficiency or pharmacological inhibition of the plasma membrane protease BACE2 enhances pancreatic β-cell function and proliferation and therefore BACE2 is a putative target for the therapeutic intervention in conditions of β-cell loss and dysfunction. To gain a molecular understanding of BACE2 function we performed a systematic and quantitative proteomic analysis to map the natural sub-strate repertoire of BACE2 and its homologue BACE1 in β-cells. Loss-and gain-of-function studies of in vitro and in vivo models identified specific and functionally heterogeneous targets. Our analysis revealed non-redundant roles of BACE1/2 in ectodomain shedding with BACE1 regulating a broader and BACE2 a more distinct set of β-cell-enriched substrates. Lastly, our study provides insights into the global β-cell sheddome and secretome, an important prerequisite to uncover novel mechanisms contributing to β-cell homeostasis and to offer a resource for therapeutic target and biomarker discoveries.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Proteomics (Schmidt)
UniBasel Contributors:Schmidt, Alexander
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Society of Biological Chemists
ISSN:0021-9258
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:21 Jun 2013 12:29
Deposited On:21 Jun 2013 12:28

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