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FK506结合蛋白12.6调节小鼠嗜铬细胞分泌
引用本文:袁琦,郭宁,顾磊,王珺,王黎,周专,姬广聚.FK506结合蛋白12.6调节小鼠嗜铬细胞分泌[J].生物化学与生物物理进展,2014,41(5):449-455.
作者姓名:袁琦  郭宁  顾磊  王珺  王黎  周专  姬广聚
作者单位:中国科学院生物物理研究所生物大分子国家重点实验室,北京 100101;中国科学院大学,北京 100049,北京大学分子医学研究所,北京 100871,中国科学院生物物理研究所生物大分子国家重点实验室,北京 100101,中国科学院生物物理研究所生物大分子国家重点实验室,北京 100101,北京大学分子医学研究所,北京 100871,北京大学分子医学研究所,北京 100871,中国科学院生物物理研究所生物大分子国家重点实验室,北京 100101
基金项目:国家重点基础研究发展计划(973)(2011CB809104)和国家自然科学基金(31271228)资助项目
摘    要:FK506结合蛋白12.6(FKBP12.6)能够结合并调控钙离子释放通道兰尼碱受体2型(RyR2)的开放,可能是儿茶酚胺分泌的重要调控器.利用FKBP12.6敲除小鼠模型,我们研究了FKBP12.6在肾上腺嗜铬细胞胞吐中的作用.结果表明,FKBP12.6在小鼠肾上腺嗜铬细胞中表达,而敲除FKBP12.6小鼠的嗜铬细胞中有正常的去极化引起的钙电流和胞吐作用.然而,FKBP12.6敲除会导致嗜铬细胞中出现增强的咖啡因引起的细胞整体钙瞬变和咖啡因引起的胞吐作用.结果提示,FKBP12.6调控肾上腺嗜铬细胞儿茶酚胺的分泌,这种调控作用是通过调节钙离子的释放而实现的.FKBP12.6是嗜铬细胞分泌的重要蛋白.

关 键 词:FK结合蛋白.  肾上腺素嗜铬细胞  儿茶酚胺  钙离子  胞吐作用
收稿时间:2014/3/13 0:00:00
修稿时间:2014/4/16 0:00:00

FKBP12.6 Regulates The Secretion of Adrenal Chromaffin Cell in Mice
YUAN Qi,GUO Ning,GU Lei,WANG Jun,WANG Li,ZHOU Zhuan and JI Guang-Ju.FKBP12.6 Regulates The Secretion of Adrenal Chromaffin Cell in Mice[J].Progress In Biochemistry and Biophysics,2014,41(5):449-455.
Authors:YUAN Qi  GUO Ning  GU Lei  WANG Jun  WANG Li  ZHOU Zhuan and JI Guang-Ju
Institution:National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;University of Chinese Academy of Sciences, Beijing 100049, China,State Key Laboratory of Biomembrane Engineering and the Centre for Life Sciences,Institute of Molecular Medicine, Peking University, Beijing 100871, China,National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China,National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China,State Key Laboratory of Biomembrane Engineering and the Centre for Life Sciences,Institute of Molecular Medicine, Peking University, Beijing 100871, China,State Key Laboratory of Biomembrane Engineering and the Centre for Life Sciences,Institute of Molecular Medicine, Peking University, Beijing 100871, China and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
Abstract:FK506 binding protein 12.6 (FKBP12.6), a protein that binds to and regulates the ryanodine receptor type 2 (RyR2) Ca2+ release channels, may act as an important regulator of catecholamine secretion. In the present study, the role of FKBP12.6 in the control of chromaffin cell exocytosis has been investigated using FKBP12.6-null mice. The results showed that FKBP12.6 was expressed in mouse chromaffin cells; deletion of FKBP12.6 did not change the depolarization induced Ca2 current and exocytosis. However, deletion of FKBP12.6 resulted in an enhanced caffeine-induced global Ca2 transient and larger caffeine-induced exocytosis in chromaffin cells of mice. These results indicate that FKBP12.6 is involved in catecholamine secretion through regulation of Ca2 release channel in mouse chromaffin cells.
Keywords:FKBP12  6  chromaffin cell  catecholamine  Ca2+  exocytosis
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