Human High Temperature Requirement Serine Protease A1 (HTRA1) Degrades Tau Protein Aggregates

Tennstaedt, A., Popsel, S., Truebestein, L., Hauske, P., Brockmann, A., Schmidt, N., Irle, I., Sacca, B., Niemeyer, C. M., Brandt, R., Ksiezak-Reding, H., Tirniceriu, A. L., Egensperger, R., Baldi, A., Dehmelt, L., Kaiser, M., Huber, Robert, Clausen, T. and Ehrmann, M. 2012. Human High Temperature Requirement Serine Protease A1 (HTRA1) Degrades Tau Protein Aggregates. Journal of Biological Chemistry 287 (25) , pp. 20931-20941. 10.1074/jbc.M111.316232

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Abstract

Protective proteases are key elements of protein quality control pathways that are up-regulated, for example, under various protein folding stresses. These proteases are employed to prevent the accumulation and aggregation of misfolded proteins that can impose severe damage to cells. The high temperature requirement A (HtrA) family of serine proteases has evolved to perform important aspects of ATP-independent protein quality control. So far, however, no HtrA protease is known that degrades protein aggregates. We show here that human HTRA1 degrades aggregated and fibrillar tau, a protein that is critically involved in various neurological disorders. Neuronal cells and patient brains accumulate less tau, neurofibrillary tangles, and neuritic plaques, respectively, when HTRA1 is expressed at elevated levels. Furthermore, HTRA1 mRNA and HTRA1 activity are up-regulated in response to elevated tau concentrations. These data suggest that HTRA1 is performing regulated proteolysis during protein quality control, the implications of which are discussed.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Subjects:	Q Science > QH Natural history > QH301 Biology
Uncontrolled Keywords:	Calpain; Caspase; Protease; Protein Degradation; Serine Protease; HTRA1; Protein Quality Control
Publisher:	American Society for Biochemistry and Molecular Biology
ISSN:	0021-9258
Last Modified:	24 Jun 2017 09:33
URI:	https://orca.cardiff.ac.uk/id/eprint/32206

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