http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
- 中文 을 입력하시려면 zhongwen을 입력하시고 space를누르시면됩니다.
- 北京 을 입력하시려면 beijing을 입력하시고 space를 누르시면 됩니다.
RISS 인기검색어
- 검색키워드
- 저자 : Gennarino, Vincenzo A. (검색결과 2 건)
- 무료
- 기관 내 무료
- 유료
-
Gennarino, Vincenzo A.,Singh, Ravi K.,White, Joshua J.,De Maio, A.,Han, K.,Kim, J.Y.,Jafar-Nejad, P.,di Ronza, A.,Kang, H.,Sayegh, Layal S.,Cooper, Thomas A.,Orr, Harry T.,Sillitoe, Roy V.,Zoghbi, Hud Cell Press ; MIT Press 2015 Cell Vol.160 No.6
Spinocerebellar ataxia type 1 (SCA1) is a paradigmatic neurodegenerative proteinopathy, in which a mutant protein (in this case, ATAXIN1) accumulates in neurons and exerts toxicity; in SCA1, this process causes progressive deterioration of motor coordination. Seeking to understand how post-translational modification of ATAXIN1 levels influences disease, we discovered that the RNA-binding protein PUMILIO1 (PUM1) not only directly regulates ATAXIN1 but also plays an unexpectedly important role in neuronal function. Loss of Pum1 caused progressive motor dysfunction and SCA1-like neurodegeneration with motor impairment, primarily by increasing Ataxin1 levels. Breeding Pum1<SUP>+/-</SUP> mice to SCA1 mice (Atxn1<SUP>154Q/+</SUP>) exacerbated disease progression, whereas breeding them to Atxn1<SUP>+/-</SUP> mice normalized Ataxin1 levels and largely rescued the Pum1<SUP>+/-</SUP> phenotype. Thus, both increased wild-type ATAXIN1 levels and PUM1 haploinsufficiency could contribute to human neurodegeneration. These results demonstrate the importance of studying post-transcriptional regulation of disease-driving proteins to reveal factors underlying neurodegenerative disease.
-
Han, Kihoon,Chen, Hogmei,Gennarino, Vincenzo A.,Richman, Ronald,Lu, Hui-Chen,Zoghbi, Huda Y. IRL Press 2015 Human molecular genetics Vol.24 No.7
<P>Silencing of fragile X mental retardation 1 (<I>FMR1</I>) gene and loss of fragile X mental retardation protein (FMRP) cause fragile X syndrome (FXS), a genetic disorder characterized by intellectual disability and autistic behaviors. FMRP is an mRNA-binding protein regulating neuronal translation of target mRNAs. Abnormalities in actin-rich dendritic spines are major neuronal features in FXS, but the molecular mechanism and identity of FMRP targets mediating this phenotype remain largely unknown. Cytoplasmic FMR1-interacting protein 2 (Cyfip2) was identified as an interactor of FMRP, and its mRNA is a highly ranked FMRP target in mouse brain. Importantly, Cyfip2 is a component of WAVE regulatory complex, a key regulator of actin cytoskeleton, suggesting that Cyfip2 could be implicated in the dendritic spine phenotype of FXS. Here, we generated and characterized <I>Cyfip2</I>-mutant (<I>Cyfip2<SUP>+/−</SUP></I>) mice. We found that <I>Cyfip2<SUP>+/−</SUP></I> mice exhibited behavioral phenotypes similar to <I>Fmr1</I>-null (<I>Fmr1<SUP>−/y</SUP></I>) mice, an animal model of FXS. Synaptic plasticity and dendritic spines were normal in <I>Cyfip2<SUP>+/−</SUP></I> hippocampus. However, dendritic spines were altered in <I>Cyfip2<SUP>+/−</SUP></I> cortex, and the dendritic spine phenotype of <I>Fmr1<SUP>−/y</SUP></I> cortex was aggravated in <I>Fmr1<SUP>−/y</SUP></I>; <I>Cyfip2<SUP>+/−</SUP></I> double-mutant mice. In addition to the spine changes at basal state, metabotropic glutamate receptor (mGluR)-induced dendritic spine regulation was impaired in both <I>Fmr1<SUP>−/y</SUP></I> and <I>Cyfip2<SUP>+/−</SUP></I> cortical neurons. Mechanistically, mGluR activation induced mRNA translation-dependent increase of Cyfip2 in wild-type cortical neurons, but not in <I>Fmr1<SUP>−/y</SUP></I> or <I>Cyfip2<SUP>+/−</SUP></I> neurons. These results suggest that misregulation of Cyfip2 function and its mGluR-induced expression contribute to the neurobehavioral phenotypes of FXS.</P>
연관 검색어 추천
이 검색어로 많이 본 자료
활용도 높은 자료
