Identification and characterization of the Drosophila tau homolog.
A pathological hallmark of neurodegenerative tauopathies, including Alzheimer's disease and a group of clinically heterogeneous frontotemporal dementias, is the presence of intracellular neurofibrillary protein lesions (reviewed in Spillantini and Goedert, TINS 10 (1998) 428). The principal component of these structures is the microtubule-associated protein tau. Although tau is normally a highly soluble protein enriched in axons, in these deposits, it is abnormally hyperphosphorylated, insoluble, and redistributed to the somatodendritic compartments of neurons. Through ultrastructual analyses, it has been determined that the tau protein in these lesions is filamentous and organized into paired-helical filaments, straight filaments, or ribbon-like filaments (Goedert et al., The Molecular and Genetic Basis of Neurological Disease (1997) 613). By the dynamic binding of microtubules, tau is thought to promote the structural stability of axons, but whether tau aggregates contribute to neurodegeneration through a direct toxicity on normal cellular functions such as organelle transport or an indirect effect on microtubule stability, is currently unknown. The identification of mutations in the tau locus in patients with familial frontotemporal dementia and Parkinsonism linked to chromosome 17 has demonstrated that mutations in tau are sufficient to cause neurodegenerative disease (Poorkaj et al., Ann. Neurol. 43 (1998) 815; Hutton et al., Nature 393 (1998) 702). To elucidate the mechanisms by which tau dysfunction contributes to neuronal loss, we have sought to model human tauopathies in a genetically tractable organism. Here we describe the isolation of a Drosophila tau cDNA (GenBank accession number AY032977), the production of antibodies that recognize the encoded protein, and their use in determining the expression and subcellular localization of the fly tau protein.
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Department of Genetics, University of Pennsylvania School of Medicine, Stellar-Chance Laboratories 709C, 422 Curie Boulevard, Philadelphia, PA 19104, USA.
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D004330:Drosophila / Q000196:embryology* / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D020271:Heredodegenerative Disorders, Nervous System / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009154:Mutation; D009420:Nervous System / Q000196:embryology / Q000254:growth & development; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
D018076:DNA, Complementary; D029721:Drosophila Proteins; D016875:tau Proteins