PMID- 10362789 OWN - NLM STAT- MEDLINE DCOM- 19990714 LR - 20240414 IS - 0002-9440 (Print) IS - 1525-2191 (Electronic) IS - 0002-9440 (Linking) VI - 154 IP - 6 DP - 1999 Jun TI - Stable expression in Chinese hamster ovary cells of mutated tau genes causing frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). PG - 1649-56 AB - Extensive neuronal loss and aggregation of tau as cytoplasmic inclusions in neurons and glial cells in selected cortical and subcortical regions is the most striking characteristic of frontotemporal dementia and parkinsonism linked to chromosome 17, which is caused by exonic or intronic mutations in the tau gene. Here, we examined the effects of four exonic mutations in four-repeat tau using stably transfected Chinese hamster ovary cells. The proportion of polymerized tubulin was the largest in the P301L transfectant. G272V and P301L transfectants showed greater instability of microtubules in the presence of Colcemid than wild-type tau, V337M, or R406W transfectants. Thus no distinct phenotypes were shared by the mutant tau transfectants with regard to microtubule assembly and stability. Unexpectedly, R406W showed low and negligible levels of phosphorylation at Thr 231 and Ser 396, respectively, in the transfectant. This presents a sharp contrast to the observation that tau aggregates in R406W-affected brains are heavily phosphorylated at these two sites. This result suggests that hyperphosphorylation at these sites cannot occur in the tau R406W bound to microtubules, and thus that the hyperphosphorylated species of tau may be generated only after disruption of microtubules. FAU - Matsumura, N AU - Matsumura N AD - Department of Neuropathology, Faculty of Medicine, University of Tokyo, Japan. FAU - Yamazaki, T AU - Yamazaki T FAU - Ihara, Y AU - Ihara Y LA - eng PT - Journal Article PL - United States TA - Am J Pathol JT - The American journal of pathology JID - 0370502 RN - 0 (tau Proteins) RN - 3CHI920QS7 (Cytochalasin B) RN - Z01IVE25KI (Demecolcine) SB - IM MH - Animals MH - Blotting, Western MH - CHO Cells MH - Chromosomes, Human, Pair 17/genetics MH - Cricetinae MH - Cytochalasin B/pharmacology MH - Demecolcine/pharmacology MH - Dementia/*genetics MH - Gene Expression MH - Genetic Linkage MH - Humans MH - Immunohistochemistry MH - Microtubules/drug effects/physiology MH - *Mutation MH - Parkinson Disease/*genetics MH - Subcellular Fractions/metabolism MH - Transfection MH - tau Proteins/*biosynthesis/*genetics/metabolism PMC - PMC1866642 EDAT- 1999/06/11 00:00 MHDA- 1999/06/11 00:01 PMCR- 1999/12/01 CRDT- 1999/06/11 00:00 PHST- 1999/06/11 00:00 [pubmed] PHST- 1999/06/11 00:01 [medline] PHST- 1999/06/11 00:00 [entrez] PHST- 1999/12/01 00:00 [pmc-release] AID - S0002-9440(10)65420-X [pii] AID - 1748 [pii] AID - 10.1016/S0002-9440(10)65420-X [doi] PST - ppublish SO - Am J Pathol. 1999 Jun;154(6):1649-56. doi: 10.1016/S0002-9440(10)65420-X.