کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8259017 | 1534629 | 2014 | 40 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Proteomic analysis of FUS interacting proteins provides insights into FUS function and its role in ALS
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کلمات کلیدی
DAPIdenaturing polyacrylamide gel electrophoresisStdevfused in sarcoma/translocated in liposarcomaRNaseSALSTBSTRIPAGSTPBSeGFP4′,6-diamidino-2-phenylindole - 4 '، 6-دیامیدینو-2-فنیلینولfamilial ALS - ALS خانوادگیsporadic ALS - ALS پراکندهBSA - BSAFUs - FUSFUS/TLS - FUS / TLSbovine serum albumin - آلبومین سرم گاوamyotrophic lateral sclerosis - اسکلروز جانبی آمیوتروفیکSDS-PAGE - الکتروفورز ژل پلی آکریل آمیدstandard deviation - انحراف معیارradioimmunoprecipitation assay buffer - بافر تست radioimmunoprecipitationALS - بیماری اسکلروز جانبی آمیوتروفیکNeurodegeneration - تولید نوروژنیکfALS - جعل اسنادribonuclease - ریبونوکلئازProtein interaction network - شبکه متقابل پروتئینwild type - نوع وحشیGene ontology - هستیشناسی ژنیProteomics - پروتئومیکسenhanced green fluorescent protein - پروتئین فلورسنت سبز افزایش یافته استStress granule - گرانول استرسglutathione S-transferase - گلوتاتیون S-ترانسفراز
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease. Mutations in the Fused in Sarcoma/Translocated in Liposarcoma (FUS/TLS) gene cause a subset of familial ALS cases and are also implicated in sporadic ALS. FUS is typically localized to the nucleus. The ALS-related FUS mutations cause cytoplasmic mis-localization and the formation of stress granule-like structures. Abnormal cytoplasmic FUS localization was also found in a subset of frontotemporal dementia (FTLD) cases without FUS mutations. To better understand the function of FUS, we performed wild-type and mutant FUS pull-downs followed by proteomic identification of the interacting proteins. The FUS interacting partners we identified are involved in multiple pathways, including chromosomal organization, transcription, RNA splicing, RNA transport, localized translation, and stress response. FUS interacted with hnRNPA1 and Matrin-3, RNA binding proteins whose mutations were also reported to cause familial ALS, suggesting that hnRNPA1 and Matrin-3 may play common pathogenic roles with FUS. The FUS interactions displayed varied RNA dependence. Numerous FUS interacting partners that we identified are components of exosomes. We found that FUS itself was present in exosomes, suggesting that the secretion of FUS might contribute to the cell-to-cell spreading of FUS pathology. FUS interacting proteins were sequestered into the cytoplasmic mutant FUS inclusions that could lead to their mis-regulation or loss of function, contributing to ALS pathogenesis. Our results provide insights into the physiological functions of FUS as well as important pathways where mutant FUS can interfere with cellular processes and potentially contribute to the pathogenesis of ALS.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1862, Issue 10, October 2016, Pages 2004-2014
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1862, Issue 10, October 2016, Pages 2004-2014
نویسندگان
Marisa Kamelgarn, Jing Chen, Lisha Kuang, Alexandra Arenas, Jianjun Zhai, Haining Zhu, Jozsef Gal,