کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5512685 | 1540439 | 2017 | 58 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Ca2+ dependent surface trafficking of norepinephrine transporters depends on threonine 30 and Ca2+ calmodulin kinases
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کلمات کلیدی
IP3dorsal ventral1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetrakis(acetoxymethyl ester)CaMKKKRHbisindolylmaleimideLDCVdesipramineDMICaMKHBSSDATFBSinositol 1,4,5-trisphosphate - inositol 1،4،5-trisphosphateMAPK - MAPKDopamine transporter - انتقال دهنده دوپامینCho - برایBAPTA/AM - بیایپیتیای / AMChinese Hamster Ovary - تخمدان هامستر چینیMin - حداقلLarge dense core vesicles - حنجره های بزرگ متراکم مرکزیNET - خالصCNS - دستگاه عصبی مرکزیminute - دقیقهfetal bovine serum - سرم جنین گاوMass spectrometry - طیف سنجی جرمیHank’s balanced salt solution - محلول نمک متعادل هانکBIM - مدلسازی اطلاعات ساختمانnorepinephrine - نوراپی نفرینhemagglutinin - هماگلوتینینAffinity - وابستگیmitogen activated protein kinase - پروتئین کیناز فعال Mitogen فعال استCa2+/calmodulin-dependent protein kinase - پروتئین کیناز وابسته به کلسیم و پتاسیم Ca2 + /Anterior-Posterior - پیش از عقب
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The antidepressant-sensitive norepinephrine (NE) transporter (NET) inactivates NE released during central and peripheral neuronal activity by transport into presynaptic cells. Altered NE clearance due to dysfunction of NET has been associated with the development of mental illness and cardiovascular diseases. NET activity in vivo is influenced by stress, neuronal activity, hormones and drugs. We investigated the mechanisms of Ca2+ regulation of NET and found that Ca2+ influenced both Vmax and Km for NE transport into cortical synaptosomes. Changes in extracellular Ca2+ triggered rapid and bidirectional surface trafficking of NET expressed in cultured cells. Deletion of residues 28-47 in the NET NH2-terminus abolished the Ca2+ effect on surface trafficking. Mutagenesis studies identified Thr30 in this region as the essential residue for both Ca2+- dependent phosphorylation and trafficking of NET. Depolarization of excitable cells increased surface NET in a Thr30 dependent manner. A proteomic analysis, RNA interference, and pharmacological inhibition supported roles of CaMKI and CaMKII in Ca2+-modulated NE transport and NET trafficking. Depolarization of primary noradrenergic neurons in culture with elevated K+ increased NET surface expression in a process that required external Ca2+ and depended on CaMK activity. Hippocampal NE clearance in vivo was also stimulated by depolarization, and inhibitors of CaMK signaling prevented this stimulation. In summary, Ca2+ signaling influenced surface trafficking of NET through a CaMK-dependent mechanism requiring Thr30.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Chemical Neuroanatomy - Volumes 83â84, October 2017, Pages 19-35
Journal: Journal of Chemical Neuroanatomy - Volumes 83â84, October 2017, Pages 19-35
نویسندگان
Uhna Sung, Francesca Binda, Valentina Savchenko, William A. Owens, Lynette C. Daws,