Tau Tubulin Kinase TTBK2 Sensitivity of Glutamate Receptor GluK2
Tau Tubulin Kinase TTBK2 Sensitivity of Glutamate Receptor GluK2
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Tau 微管蛋白激酶 TTBK2 谷氨酸受体 GluK2 的敏感性
DOI：
10.1159/000447847
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发表时间：
2016
影响因子：
--
通讯作者：
Strutz-Seebohm
中科院分区：
文献类型：
--
作者：
Nieding;Matschke;Seebohm;Strutz-Seebohm
背景/目的遗传性、常染色体显性遗传性脊髓小脑共济失调11型（SCA 11）是由TTBK 2（tau微管蛋白激酶2）功能缺失突变引起的。在SCA 11患者中观察到的突变包括截短的TTBK 2（450）。本研究探讨了TTBK 2对谷氨酸受体GluK 2功能的影响。方法在不表达野生型TTBK 2、TTBK 2（450）截短突变体、TTBK 2（KD）和TTBK 2（450/KD）的条件下，在非洲爪蟾卵母细胞中表达GluK 2。GluK 2电流测定双电极电压钳和GluK 2蛋白丰度在细胞膜利用共聚焦microscopic.ResultsGluK2表达卵母细胞产生的电流，这是显着低于在卵母细胞表达GluK 2与TTBK 2 wt或TTBK 2（KD）比单独或与TTBK 2（450）或TTBK 2（450/KD）。根据EGFP标记的GluK 2的共聚焦显微镜，TTBK 2 wt降低了细胞膜中GluK 2蛋白的丰度。结论TTBK 2通过减少细胞膜上受体蛋白的丰度，下调GluK 2的活性，可能是其抗神经兴奋性毒性的机制之一。
Background/AimsInherited, autosomal dominant spinocerebellar ataxia type 11 (SCA11) is caused by loss of function mutations of TTBK2 (tau tubulin kinase 2). Mutations observed in patients with SCA11 include truncated TTBK2 (450). The present study explored the possibility that TTBK2 influences the function of the glutamate receptor GluK2.MethodsGluK2 was expressed in Xenopus oocytes without and with additional expression of wild type TTBK2, the truncated mutant TTBK2 (450), or the kinase dead mutants TTBK2 (KD) and TTBK2 (450/KD). GluK2 current was determined by dual electrode voltage clamp and GluK2 protein abundance in the cell membrane utilizing confocal microscopy.ResultsGlutamate exposure of GluK2 expressing oocytes generated a current, which was significantly lower in oocytes expressing GluK2 together with TTBK2 wt or TTBK2 (KD) than in oocytes expressing GluK2 alone or together with either TTBK2 (450) or TTBK2 (450/KD). According to confocal microscopy of EGFP-tagged GluK2, TTBK2 wt decreased the GluK2 protein abundance in the cell membrane. Overexpression of an inactive RAB5 (N133I) mutant but not RAB5wt could reverse the TTBK2 effect on GluK2 suggesting that RAB5 function is required for the effect.ConclusionsTTBK2 down-regulates GluK2 activity by decreasing the receptor protein abundance in the cell membrane via RAB5-dependent endocytosis, an effect that may protect against neuroexcitotoxicity.
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影响因子：
--
作者：
Liao JC;Yang TT;Weng RR;Kuo CT;Chang CW
通讯作者：
Chang CW
勘误表：TTBK2 突变，编码与 tau 磷酸化有关的激酶，与脊髓小脑共济失调 11 型分离
影响因子：
30.8
作者：
H. Houlden;Janel O. Johnson;C. Gardner‐Thorpe;T. Lashley;D. Hernandez;P. Worth;A. Singleton;D. Hilton;J. Holton;T. Révész;M. Davis;P. Giunti;N. Wood
通讯作者：
N. Wood
DOI：
10.1172/jci15420
发表时间：
2002-06
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
A. Choudhury;M. Dominguez;V. Puri;D. Sharma;K. Narita;C. Wheatley;D. Marks;R. Pagano
通讯作者：
A. Choudhury;M. Dominguez;V. Puri;D. Sharma;K. Narita;C. Wheatley;D. Marks;R. Pagano
影响因子：
4.5
作者：
Seebohm, Guiscard;Wrobel, Eva;Pusch, Michael;Dicks, Markus;Terhag, Jan;Matschke, Veronika;Rothenberg, Ina;Ursu, Oana N.;Hertel, Fabian;Pott, Lutz;Lang, Florian;Schulze-Bahr, Eric;Hollmann, Michael;Stoll, Raphael;Strutz-Seebohm, Nathalie
通讯作者：
Strutz-Seebohm, Nathalie
影响因子：
6.8
作者：
Kawasaki, M;Nakayama, K;Wakatsuki, S
通讯作者：
Wakatsuki, S