Beta catenin is regulated by its subcellular distribution and mutant huntingtin status in Huntington's disease cell STHdhQ111/HdhQ111
- Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata, 700064 (India)
Highlights: • Mutant Htt gain-of-function in Q111 cell increases miR-214 & decreases beta catenin. • Mutant Htt function in Q111 cell is aggregate independent. • Aggregate forming mutant Htt construct 83Q-DsRed increases beta catenin in Q7 cell. • Cytosolic localization of beta catenin in Q111 cell aids to its phosphorylation. Dysregulation of gene expression at RNA and protein level is a hallmark of Huntington's disease (HD). Altered levels of microRNAs and beta catenin in HD were studied earlier; however, any direct involvement of full length, basally-expressing mutant huntingtin (Htt) remained to be elusive. Here we reported that the gain-of-function mutation of full-length basally-expressing Htt in HD cell Q111 (STHdhQ111/HdhQ111) upregulated microRNA-214 and decreased beta catenin & its transcriptional activity in an aggregate-independent manner. The result was quite opposite of the function of aggregate-forming mutant Htt fragment 83Q-DsRed. Here, we also reported an elevated level of beta catenin phosphorylation in Q111 cell compared to Q7 cell (SThdhQ7/HdhQ7). We showed that in Q111 cell (compared to Q7), beta catenin was more localized in the cytosol than that of the plasma membrane. This is significant as Gsk3beta phosphorylates beta catenin in the cytosol. Hence, for the first time, our study identified beta catenin localization and mutant Htt status as two key factors of beta catenin regulation in HD.
- OSTI ID:
- 23136948
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 503; ISSN 0006-291X; ISSN BBRCA9
- Country of Publication:
- United States
- Language:
- English
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