کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10815939 | 1058530 | 2015 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
PDZK1/NHERF3 Differentially Regulates Corticotropin-releasing Factor Receptor 1 and Serotonin 2A Receptor Signaling and Endocytosis
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کلمات کلیدی
PDZCRF receptor 2synapse-associated protein 975-HT2CRSAP97CRF receptor 15-HT2ARHEK 293β2ARSyngap1GRKCRFR1serotonin receptor 2ASSTRGKAPCRFR25-HTGPCRNMDARCRF5-HT2A Receptor - 5-HT2A گیرنده5-HT2C receptor - 5-HT2C گیرندهERK1/2 - ERK1 / 2G protein-coupled receptor kinase - G پروتئین گیرنده کینازMAPK - MAPKmood disorders - اختلال خلقیanalysis of variance - تحلیل واریانسANOVA - تحلیل واریانس Analysis of varianceProtein interaction - تعامل پروتئینSerotonin - سروتونینSignaling - سیگنالینگShank - شانکcorticotropin-releasing factor - عامل تخریب کورتیکوتروپینTrafficking - قاچاقhemagglutinin - هماگلوتینینguanylate kinase-associated protein - پروتئین مرتبط با گینیلات کینازmitogen-activated protein kinase - پروتئین کیناز فعال با mitogenhuman embryonic kidney 293 - کلیه جنینی انسان 293extracellular signal-regulated kinase - کیناز تنظیم شده سیگنال خارج سلولیN-methyl-d-aspartate receptor - گیرنده N-methyl-d-aspartateβ2-adrenergic receptor - گیرنده β2-adrenergicSomatostatin receptor - گیرنده سوماتوستاتینG protein-coupled receptor - گیرندههای جفتشونده با پروتئین جی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The corticotropin-releasing factor receptor 1 (CRFR1) and serotonin 2A receptor (5-HT2AR) are linked to cellular mechanisms underlying stress anxiety and depression. Both receptors are members of the G protein-coupled receptor (GPCR) superfamily and encode class I PSD-95/DiscsLarge/Zona Occludens 1 (PDZ) binding motifs (-S/T-x-V/I/L) at the end of their carboxyl-terminal tails. We have identified PDZK1, also referred to as Na(+)/H(+) exchange regulatory cofactor 3 (NHERF3) as both a CRFR1- and 5-HT2AR-interacting protein. We have examined whether PDZK1 plays a role in regulating both CRFR1 and 5-HT2AR activity. We find that while PDZK1 interactions with CRFR1 are PDZ binding motif-dependent, PDZK1 associates with 5-HT2AR in a PDZ binding motif-independent manner and CRFR1 expression, but not 5-HT2AR expression, redistributes PDZK1 to the plasma membrane in PDZ binding motif-dependent manner. PDZK1, negatively regulates 5-HT2AR endocytosis and has no effect upon 5-HT2AR-mediated ERK1/2 phosphorylation. In contrast, PDZK1 overexpression does not affect CRFR1 endocytosis, but selectively increases CRFR1-stimulated ERK1/2 phosphorylation. Similar to what has been previously reported for PSD-95 and SAP97, PDZK1 positively influences 5-HT2AR-stimulated inositol phosphate formation, but does not contribute to the regulation of CRFR1-mediated cAMP signaling. Taken together, these results indicate that PDZK1 differentially regulates the signaling and trafficking of CRFR1 and 5-HT2AR via PDZ-dependent and -independent mechanisms, respectively.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 27, Issue 3, March 2015, Pages 519-531
Journal: Cellular Signalling - Volume 27, Issue 3, March 2015, Pages 519-531
نویسندگان
Cornelia Walther, Fabiana A. Caetano, Henry A. Dunn, Stephen S.G. Ferguson,