Downregulation of the Creatine Transporter SLC6A8 by JAK2

被引：0
作者：
Manzar Shojaiefard
Zohreh Hosseinzadeh
Shefalee K. Bhavsar
Florian Lang
机构：
[1] University of Tübingen,Department of Physiology I
[2] Fasa University of Medical Science,Department of Physiology
[3] Shahid Chamran University,Department of Science
来源：
The Journal of Membrane Biology | 2012年 / 245卷
关键词：
Creatine uptake; Energy depletion; Brefeldin; AG490; Erythropoietin; Leptin;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Janus-activated kinase-2 (JAK2) participates in the regulation of the Na+-coupled glucose transporter SGLT1 and the Na+-coupled amino acid transporter SLC6A19. Concentrative cellular creatine uptake is similarly accomplished by Na+-coupled transport. The carrier involved is SLC6A8 (CreaT). The present study thus explored whether JAK2 regulates the activity of SLC6A8. To this end, cRNA encoding SLC6A8 was injected into Xenopus oocytes with or without cRNA encoding wild-type JAK2, constitutively active V617FJAK2 or inactive K882EJAK2. Electrogenic creatine transport was determined in those oocytes by dual-electrode voltage-clamp experiments. In oocytes injected with cRNA encoding SLC6A8 but not in oocytes injected with water or with cRNA encoding JAK2 alone, addition of 1 mM creatine to the extracellular bath generated an inward current (Icrea). In SLC6A8 expressing oocytes Icrea was significantly decreased by coexpression of JAK2 or V617FJAK2 but not by coexpression of K882EJAK2. According to kinetic analysis, coexpression of JAK2 decreased the maximal transport rate without significantly modifying the affinity of the carrier. In oocytes expressing SLC6A8 and V617FJAK2 Icrea was gradually increased by the JAK2 inhibitor AG490 (40 μM). In SLC6A8 and JAK2 coexpressing oocytes the decline of Icrea following disruption of carrier insertion with brefeldin A (5 μM) was similar in the absence and presence of JAK2. In conclusion, JAK2 is a novel regulator of the creatine transporter SLC6A8, which downregulates the carrier, presumably by interference with carrier protein insertion into the cell membrane.
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页码：157 / 163
页数：6
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