PMID- 20377816
OWN - NLM
STAT- MEDLINE
DCOM- 20100715
LR  - 20191210
IS  - 1479-8301 (Electronic)
IS  - 1346-3500 (Linking)
VI  - 9
IP  - 4
DP  - 2009 Dec
TI  - 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.
PG  - 157-66
LID - 10.1111/j.1479-8301.2010.00307.x [doi]
AB  - 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.
FAU - Yanagi, Kentaro
AU  - Yanagi K
AD  - Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, 
      Osaka, Japan.
FAU - Tanaka, Toshihisa
AU  - Tanaka T
FAU - Kato, Kiyoko
AU  - Kato K
FAU - Sadik, Golam
AU  - Sadik G
FAU - Morihara, Takashi
AU  - Morihara T
FAU - Kudo, Takashi
AU  - Kudo T
FAU - Takeda, Masatoshi
AU  - Takeda M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Psychogeriatrics
JT  - Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society
JID - 101230058
RN  - 0 (MAPT protein, human)
RN  - 0 (tau Proteins)
RN  - EC 3.4.11.- (Aminopeptidases)
RN  - EC 3.4.11.14 (enkephalin degrading enzyme)
SB  - IM
MH  - *Alleles
MH  - Aminopeptidases/*genetics
MH  - Animals
MH  - COS Cells
MH  - Cell Death/genetics
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - Chlorocebus aethiops
MH  - *Chromosome Mapping
MH  - Chromosomes, Human, Pair 17/*genetics
MH  - *DNA Mutational Analysis
MH  - Frontotemporal Dementia/diagnosis/*genetics
MH  - Humans
MH  - Tauopathies/diagnosis/*genetics
MH  - Transfection
MH  - tau Proteins/*genetics
EDAT- 2010/04/10 06:00
MHDA- 2010/07/16 06:00
CRDT- 2010/04/10 06:00
PHST- 2010/04/10 06:00 [entrez]
PHST- 2010/04/10 06:00 [pubmed]
PHST- 2010/07/16 06:00 [medline]
AID - PSY307 [pii]
AID - 10.1111/j.1479-8301.2010.00307.x [doi]
PST - ppublish
SO  - Psychogeriatrics. 2009 Dec;9(4):157-66. doi: 10.1111/j.1479-8301.2010.00307.x.