Reference Report

Reference
Citation	Fulga, T.A., Elson-Schwab, I., Khurana, V., Steinhilb, M.L., Spires, T.L., Hyman, B.T., Feany, M.B. (2007). Abnormal bundling and accumulation of F-actin mediates tau-induced neuronal degeneration in vivo. Nat. Cell Biol. 9(2): 139--148. (Export to RIS)
FlyBase ID	FBrf0193954
Publication Type	Research paper
PubMed ID	17187063
PubMed Abstract	Hyperphosphorylated forms of the microtubule-associated protein (MAP) tau accumulate in Alzheimer's disease and related tauopathies and are thought to have an important role in neurodegeneration. However, the mechanisms through which phosphorylated tau induces neurodegeneration have remained elusive. Here, we show that tau-induced neurodegeneration is associated with accumulation of filamentous actin (F-actin) and the formation of actin-rich rods in Drosophila and mouse models of tauopathy. Importantly, modulating F-actin levels genetically leads to dramatic modification of tau-induced neurodegeneration. The ability of tau to interact with F-actin in vivo and in vitro provides a molecular mechanism for the observed phenotypes. Finally, we show that the Alzheimer's disease-linked human beta-amyloid protein (Abeta) synergistically enhances the ability of wild-type tau to promote alterations in the actin cytoskeleton and neurodegeneration. These findings raise the possibility that a direct interaction between tau and actin may be a critical mediator of tau-induced neurotoxicity in Alzheimer's disease and related disorders.
DOI	10.1038/ncb1528
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Nat. Cell Biol.
Title	Nature Cell Biology
Publication Year	1999-
ISBN/ISSN	1465-7392 1476-4679
Data from Reference
Alleles (11)
	Act5C^G0010 Act5C^{Scer\UAS.T:Avic\GFP} Hsap\APP^{Aβ42.Scer\UAS} Hsap\MAPT^AP.Scer\UAS Hsap\MAPT^E14.Scer\UAS Hsap\MAPT^{R406W.Scer\UAS} Hsap\MAPT^Scer\UAS.cWa Hsap\MAPT^{V337M.Scer\UAS} Scer\GAL4^elav.PLu Scer\GAL4^GMR.PF tsr^{Scer\UAS.T:Zzzz\His6}
Constructs (10)
	P{GAL4-elav.L} P{GAL4-ninaE.GMR} P{UAS-Act5C.T:GFP} P{UAS-APP.Aβ42} P{UAS-Hsap\MAPT.AP} P{UAS-Hsap\MAPT.E14} P{UAS-Hsap\MAPT.R406W} P{UAS-Hsap\MAPT.V337M} P{UAS-Hsap\MAPT.W} P{UAS-tsr.His}
Genes (5)
	Act5C Hsap\APP Hsap\MAPT Scer\GAL4 tsr
Natural transposons (1)
	P-element