ArticleThe Journal of biological chemistry2009
Familial FTDP-17 missense mutations inhibit microtubule assembly-promoting activity of tau by increasing phosphorylation at Ser202 in vitro.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- α-synuclein and tau: interactions, cross-seeding, and the redefinition of synucleinopathies as complex proteinopathies.Frontiers in neuroscience · 2025Review
- HS3ST2 expression induces the cell autonomous aggregation of tau.Scientific reports · 2022Article
- Intranasal Administration of Nanovectorized Docosahexaenoic Acid (DHA) Improves Cognitive Function in Two Complementary Mouse Models of Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2022Article
- Impact of the Hereditary P301L Mutation on the Correlated Conformational Dynamics of Human Tau Protein Revealed by the Paramagnetic Relaxation Enhancement NMR Experiments.International journal of molecular sciences · 2020Article
- Analysis of mutations in primary and metastatic synovial sarcoma.Oncotarget · 2018Article
- Hyperphosphorylation of Tau Associates With Changes in Its Function Beyond Microtubule Stability.Frontiers in cellular neuroscience · 2018Review
- Article
- Cellular factors modulating the mechanism of tau protein aggregation.Cellular and molecular life sciences : CMLS · 2015Review
- A novel triple repeat mutant tau transgenic model that mimics aspects of pick's disease and fronto-temporal tauopathies.PloS one · 2015Article
- Hypoxia alters expression of zebrafish microtubule-associated protein tau (mapta, maptb) gene transcripts.BMC research notes · 2014Article
- Anti-dementia Activity of Nobiletin, a Citrus Flavonoid: A Review of Animal Studies.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2014Review
- Physiological and pathological phosphorylation of tau by Cdk5.Frontiers in molecular neuroscience · 2014Review
- Protein phosphorylation in neurodegeneration: friend or foe?Frontiers in molecular neuroscience · 2014Review
- Article
- Chaperone-dependent Neurodegeneration: A Molecular Perspective on Therapeutic Intervention.Journal of Alzheimer's disease & Parkinsonism · 2013Article
- Article
- Stable mutated tau441 transfected SH-SY5Y cells as screening tool for Alzheimer's disease drug candidates.Journal of molecular neuroscience : MN · 2012Article
- The neuroprotective disease-modifying potential of psychotropics in Parkinson's disease.Parkinson's disease · 2012Article
- Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation.Human molecular genetics · 2011Article
- Early growth response 1 (Egr-1) regulates phosphorylation of microtubule-associated protein tau in mammalian brain.The Journal of biological chemistry · 2011Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In Alzheimer disease (AD), frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) and other tauopathies, tau accumulates and forms paired helical filaments (PHFs) in the brain. Tau isolated from PHFs is phosphorylated at a number of sites, migrates as approximately 60-, 64-, and 68-kDa bands on SDS-gel, and does not promote microtubule assembly. Upon dephosphorylation, the PHF-tau migrates as approximately 50-60-kDa bands on SDS-gels in a manner similar to tau that is isolated from normal brain and promotes microtubule assembly. The site(s) that inhibits microtubule assembly-promoting activity when phosphorylated in the diseased brain is not known. In this study, when tau was phosphorylated by Cdk5 in vitro, its mobility shifted from approximately 60-kDa bands to approximately 64- and 68-kDa bands in a time-dependent manner. This mobility shift correlated with phosphorylation at Ser(202), and Ser(202) phosphorylation inhibited tau microtubule-assembly promoting activity. When several tau point mutants were analyzed, G272V, P301L, V337M, and R406W mutations associated with FTDP-17, but not nonspecific mutations S214A and S262A, promoted Ser(202) phosphorylation and mobility shift to a approximately 68-kDa band. Furthermore, Ser(202) phosphorylation inhibited the microtubule assembly-promoting activity of FTDP-17 mutants more than of WT. Our data indicate that FTDP-17 missense mutations, by promoting phosphorylation at Ser(202), inhibit the microtubule assembly-promoting activity of tau in vitro, suggesting that Ser(202) phosphorylation plays a major role in the development of NFT pathology in AD and related tauopathies.
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