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Dysfunction of the neuronal RNA binding protein RBFOX1 has been linked to epilepsy and autism spectrum disorders. Rbfox1 loss in mice leads to neuronal hyper-excitability and seizures, but the physiological basis for this is unknown. We identify the vSNARE protein Vamp1 as a major Rbfox1 target. Vamp1 is strongly downregulated in Rbfox1 Nes-cKO mice due to loss of 3′ UTR binding by RBFOX1. Cytoplasmic...
Gamma-aminobutyric acid (GABA) is the main chemical inhibitory neurotransmitter in the brain. In the central nervous system, it acts on two distinct types of receptor: an ion channel, that is, an “ionotropic” receptor permeable to Cl − and HCO 3− (GABA A receptors [GABA A Rs]) and a G-protein coupled “metabotropic” receptor that is linked to various effector mechanisms...
Expanded polyglutamine (polyQ) proteins in Huntington’s disease (HD) as well as other polyQ disorders are known to elicit a variety of intracellular toxicities, but it remains unclear whether polyQ proteins can elicit pathological cell-cell interactions which are critical to disease pathogenesis. To test this possibility, we have created conditional HD mice expressing a neuropathogenic form of mutant...
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