+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Involvement of puromycin-sensitive aminopeptidase in proteolysis of tau protein in cultured cells, and attenuated proteolysis of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) mutant tau



Involvement of puromycin-sensitive aminopeptidase in proteolysis of tau protein in cultured cells, and attenuated proteolysis of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) mutant tau



Psychogeriatrics 9(4): 157-166



In tauopathies, tau protein is hyperphosphorylated, ubiquitinated, and accumulated in the brain; however, the mechanisms underlying this accumulation remain unclear. To gain an understanding of the role of proteases in the metabolism of tau protein, in the present study we evaluated the effects of protease inhibitors in SH-SY5Y human neuroblastoma cells and COS-7 cells transfected with the tau gene. When cells were treated with 0.1-10 micromol/L of lactacystin and 1.0-20 micromol/L of MG-132 (inhibitors of proteasome), 0.1-10 micromol/L of CA-074Me (a cathepsin inhibitor), and 0.1-2 micromol/L of puromycin (a puromycin-sensitive aminopeptidase (PSA) inhibitor) for up to 24 h, there were no significant changes in tau protein levels. However, pulse-chase experiments demonstrated that the proteolysis of tau protein in SH-SY5Y cells was attenuated following treatment of cells with 200 nmol/L puromycin. Increased tau protein levels were also observed in SH-SY5Y cells treated with short interference (si) RNA to PSA to inhibit the expression of PSA. These data suggest that PSA is a protease that catalyses tau protein predominantly in SH-SY5Y cells. The protein metabolism of tau-containing mutations of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) was also investigated using pulse-chase experiments. The results indicate attenuated proteolysis of tau in cells transfected with mutant tau genes after 48 h. Further immunocytochemical analysis and subcellular fractionation experiments revealed that the mutations did not alter the intracellular distribution of tau and suggested that impaired accessibility of tau to PSA is unlikely to account for the attenuated proteolysis of tau protein. Western blotting with phosphorylation-dependent antibodies revealed that phosphorylation levels of tau at Thr(231), Ser(396), and Ser(409) were increased in cells transfected with V337M, R406W, and R406W mutant tau genes, respectively. Together, the data suggest that attenuated proteolysis of FTDP-17 mutant tau may be explained by increased phosphorylation levels, resulting in resistance to proteolysis.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 053978031

Download citation: RISBibTeXText

PMID: 20377816

DOI: 10.1111/j.1479-8301.2010.00307.x


Related references

Refining frontotemporal dementia with parkinsonism linked to chromosome 17: introducing FTDP-17 (MAPT) and FTDP-17 (PGRN). Archives of Neurology 65(4): 460-464, 2008

Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). No to Shinkei 52(2): 127-132, 2000

Molecular genetics of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Folia Neuropathologica 40(3): 111-118, 2002

Tau gene mutations in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Neurogenetics 2(4): 193-205, 2000

Molecular biology of FTDP-17 (frontotemporal dementia and parkinsonism linked to chromosome 17). Nihon Rinsho. Japanese Journal of Clinical Medicine 69 Suppl 10 Pt 2: 379-383, 2011

Stable expression in Chinese hamster ovary cells of mutated tau genes causing frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). American Journal of Pathology 154(6): 1649-1656, 1999

Japanese contribution to the understanding of frontotemporal dementia and parkinsonism linked to chromosome 17(FTDP-17). No to Shinkei 55(2): 107-119, 2003

Comparison of extent of tau pathology in patients with frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), frontotemporal lobar degeneration with Pick bodies and early onset Alzheimer's disease. Neuropathology and Applied Neurobiology 32(4): 374-387, 2006

Clinical, genetic and pathological aspects of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Rinsho Shinkeigaku 44(11): 875-878, 2004

Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17): PPND family. A longitudinal videotape demonstration. Movement Disorders 16(4): 756-760, 2001

The genetics of dementias. Part 1: Molecular basis of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Postepy Higieny i Medycyny Doswiadczalnej 63: 278-286, 2009

Tau gene mutations in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Their relevance for understanding the neurogenerative process. Annals of the new York Academy of Sciences 920: 74-83, 2000

Neuropathological features of frontotemporal dementia and parkinsonism linked to chromosome 17q21-22 (FTDP-17): Duke Family 1684. Journal of Neuropathology and Experimental Neurology 58(8): 859-866, 1999