کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1983424 | 1539883 | 2015 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
PTPN21 exerts pro-neuronal survival and neuritic elongation via ErbB4/NRG3 signaling
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کلمات کلیدی
eQTLKIF1CP-TyrQuantitative reverse transcriptase-PCRRTKErbB4RT-qPCRFAKSNPsETK - اثرElk-1 - الک-1Expression quantitative trait locus - بیان صفات کمی صفاتImmunoprecipitation - تخریب ایمنیTyrosine phosphatase - تریروزین فسفاتازRTK, Receptor tyrosine kinase - تیروزین کینازهای گیرنده ایGenome-wide association study - مطالعه مرتبط با ژنومGWAS - مطالعهٔ همخوانی سراسر ژنومSingle nucleotide polymorphisms - پلیمورفیسم تک نوکلئوتیدیfocal adhesion kinase - کیناز چسبندگی کانونی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Although expression quantitative trait locus, eQTL, serves as an explicit indicator of gene-gene associations, challenges remain to disentangle the mechanisms by which genetic variations alter gene expression. Here we combined eQTL and molecular analyses to identify an association between two seemingly non-associated genes in brain expression data from BXD inbred mice, namely Ptpn21 and Nrg3. Using biotinylated receptor tracking and immunoprecipitation analyses, we determined that PTPN21 de-phosphorylates the upstream receptor tyrosine kinase ErbB4 leading to the up-regulation of its downstream signaling. Conversely, kinase-dead ErbB4 (K751R) or phosphatase-dead PTPN21 (C1108S) mutants impede PTPN21-dependent signaling. Furthermore, PTPN21 also induced Elk-1 activation in embryonic cortical neurons and a novel Elk-1 binding motif was identified in a region located 1919Â bp upstream of the NRG3 initiation codon. This enables PTPN21 to promote NRG3 expression through Elk-1, which provides a biochemical mechanism for the PTPN21-NRG3 association identified by eQTL. Biologically, PTPN21 positively influences cortical neuronal survival and, similar to Elk-1, it also enhances neuritic length. Our combined approaches show for the first time, a link between NRG3 and PTPN21 within a signaling cascade. This may explain why these two seemingly unrelated genes have previously been identified as risk genes for schizophrenia.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The International Journal of Biochemistry & Cell Biology - Volume 61, April 2015, Pages 53-62
Journal: The International Journal of Biochemistry & Cell Biology - Volume 61, April 2015, Pages 53-62
نویسندگان
Janice Hiu-Chor Plani-Lam, Tai-Cheong Chow, Kam-Leung Siu, Wing Hin Chau, Ming-Him James Ng, Suying Bao, Cheung Toa Ng, Pak Sham, Daisy Kwok-Yan Shum, Evan Ingley, Dong-Yan Jin, You-Qiang Song,