Spinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disease that results from abnormal expansion of a polyglutamine (polyQ) repeat. SCA6 is caused by CAG triplet repeat expansion in the gene CACNA1A, resulting in a polyQ tract of 19-33 in patients. CACNA1A, a bicistronic gene, encodes the α1A calcium channel subunit and the transcription factor, α1ACT. PolyQ expansion in α1ACT causes degeneration in mice. We recently described the first Drosophila models of SCA6 that express α1ACT with a normal (11Q) or hyper-expanded (70Q) polyQ. Here, we report additional α1ACT transgenic flies, which express full-length α1ACT with a 33Q repeat. We show that α1ACT33Q is toxic in Drosophila, but less so than the 70Q version. When expressed everywhere, α1ACT33Q-expressing adults die earlier than flies expressing the normal allele. α1ACT33Q causes retinal degeneration and leads to aggregated species in an age-dependent manner, but at a slower pace than the 70Q counterpart. According to western blots, α1ACT33Q localizes less readily in the nucleus than α1ACT70Q, providing clues into the importance of polyQ tract length on α1ACT localization and its site of toxicity. We expect that these new lines will be highly valuable for future work on SCA6.
In the title compound, [Cu(C4H2O4)(C11H9N3O)2(H2O)] n , Cu(II) ions on crystallographic twofold rotation axes are coordinated in a square pyramidal environment by two trans O atoms belonging to two monodentate fumarate anions, two trans isonicotinamide pyridyl N-donor atoms from monodentate, pendant 3-pyridyl-isonicotinamide (3-pina) ligands, and one apical aqua ligand, also sited on the crystallographic twofold rotation axis. The exobidentate fumarate ligands form [Cu(fumar-ate)(3-pina)2(H2O)] n coordination polymer chains that are arranged parallel to [001]. In the crystal, these polymeric chains are anchored into supra-molecular layers parallel to (100) by O-Hâ¯O hydrogen bonds between aqua ligands and unligating fumarate O atoms, and N-Hâ¯O(=C) hydrogen bonds between 3-pina ligands. In turn, the layers aggregate by weak C-Hâ¯N and C-Hâ¯O hydrogen bonds, affording a three-dimensional network.
