Reference Report

Reference
Citation	Tsuda, H., Jafar-Nejad, H., Patel, A.J., Sun, Y., Chen, H.K., Rose, M.F., Venken, K.J., Botas, J., Orr, H.T., Bellen, H.J., Zoghbi, H.Y. (2005). The AXH domain of Ataxin-1 mediates neurodegeneration through its interaction with Gfi-1/Senseless proteins. Cell 122(4): 633--644. (Export to RIS)
FlyBase ID	FBrf0187241
Publication Type	Research paper
PubMed ID	16122429
PubMed Abstract	Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease caused by an expanded glutamine tract in human Ataxin-1 (hAtx-1). The expansion stabilizes hAtx-1, leading to its accumulation. To understand how stabilized hAtx-1 induces selective neuronal degeneration, we studied Drosophila Atx-1 (dAtx-1), which has a conserved AXH domain but lacks a polyglutamine tract. Overexpression of hAtx-1 in fruit flies produces phenotypes similar to those of dAtx-1 but different from the polyglutamine peptide alone. We show that the Drosophila and mammalian transcription factors Senseless/Gfi-1 interact with Atx-1's AXH domain. In flies, overexpression of Atx-1 inhibits sensory-organ development by decreasing Senseless protein. Similarly, overexpression of wild-type and glutamine-expanded hAtx-1 reduces Gfi-1 levels in Purkinje cells. Deletion of the AXH domain abolishes the effects of glutamine-expanded hAtx-1 on Senseless/Gfi-1. Interestingly, loss of Gfi-1 mimics SCA1 phenotypes in Purkinje cells. These results indicate that the Atx-1/Gfi-1 interaction contributes to the selective Purkinje cell degeneration in SCA1.
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Cell
Title	Cell
Publication Year	1974-
ISBN/ISSN	0092-8674
Data from Reference
Alleles (18)
	ac^Act5C.PJ Atx-1^Scer\UAS.cTa da^Act5C.PJ Ecol\lacZ^Scer\UAS.cUa Hsap\ATXN1^30Q.Scer\UAS Hsap\ATXN1^82Q.Scer\UAS Mmus\Cd8a^{Scer\UAS.T:Avic\GFP} Ppyr\LUC^ac.470 Scer\GAL4^bbg-C96 Scer\GAL4^C5 Scer\GAL4^dpp.blk1 Scer\GAL4^GMR.PF Scer\GAL4^ninaE.PT Scer\GAL4^sca-109-68 Scer\GAL4^Scer\UAS.cHa sens^Act5C.PJ sens^Scer\UAS.cNa Zzzz\CAG^{127Q.Scer\UAS.T:Ivir\HA1}
Constructs (11)
	P{GAL4-dpp.blk1} P{GAL4-ninaE.GMR} P{rh1-GAL4} P{UAS-Atx-1.T} P{UAS-Gal4.H} P{UAS-Hsap\ATX1.30Q} P{UAS-Hsap\ATX1.82Q} P{UAS-lacZ.U} P{UAS-mCD8::GFP.L} P{UAS-sens.N} P{UAS-Zzzz\CAG.127Q}
Genes (14)
	ac Atx-1 Cbp53E da Ecol\lacZ Hsap\ATXN1 Mmus\Cd8a Ppyr\LUC Scer\GAL4 sens T:Avic\GFP T:Ivir\HA1 wg Zzzz\CAG
Insertions (3)
	P{GawB}bbg^C96 P{GawB}C5^C5 P{GawB}sca^109-68
Natural transposons (1)
	P-element