| First Author | Marcora E | Year | 2010 |
| Journal | Hum Mol Genet | Volume | 19 |
| Issue | 22 | Pages | 4373-84 |
| PubMed ID | 20739295 | Mgi Jnum | J:165147 |
| Mgi Id | MGI:4836326 | Doi | 10.1093/hmg/ddq358 |
| Citation | Marcora E, et al. (2010) The Huntington's disease mutation impairs Huntingtin's role in the transport of NF-kappaB from the synapse to the nucleus. Hum Mol Genet 19(22):4373-84 |
| abstractText | Expansion of a polyglutamine (polyQ) tract in the Huntingtin (Htt) protein causes Huntington's disease (HD), a fatal inherited neurodegenerative disorder. Loss of the normal function of Htt is thought to be an important pathogenetic component of HD. However, the function of wild-type Htt is not well defined. Htt is thought to be a multifunctional protein that plays distinct roles in several biological processes, including synaptic transmission, intracellular transport and neuronal transcription. Here, we show with biochemical and live cell imaging studies that wild-type Htt stimulates the transport of nuclear factor kappa light-chain-enhancer of activated B cells (NF-kappaB) out of dendritic spines (where NF-kappaB is activated by excitatory synaptic input) and supports a high level of active NF-kappaB in neuronal nuclei (where NF-kappaB stimulates the transcription of target genes). We show that this novel function of Htt is impaired by the polyQ expansion and thus may contribute to the etiology of HD. |
