对于长期以来寻求的调节分泌的离子分离器,染色素B的分子要求
Gaya P Yadav1, Mani Annamalai2, D Walker Hagan3
1Departments of Microbiology and Cell Science, and Medicinal Chemistry, University of Florida, Gainesville, FL 32611, USA; Departments of Materials Design and Innovation and HWI, State University of New York at Buffalo, Buffalo, NY 14201, USA; Currently at the Department of Biochemistry & Biophysics, Texas A&M University, 300 Olsen Blvd, College Station, TX 77843, USA.
染色素B (CHGB) 作为分泌颗粒中的关键离子分离器,对神经内分泌细胞功能至关重要. 它的道活动调节颗粒酸性,货物处理和脊椎动物的激素分泌.
科学领域:
- 细胞生物学 细胞生物学
- 神经内分泌学神经内分泌学
- 分子生理学分子生理学
背景情况:
- 在真核生物中,受调节的分泌依赖于分泌颗粒内的分子信号.
- 几十年来,分泌颗粒中的离子分离电导的生物化学特征一直是难以捉摸的.
- 之前的候选CLC-3在实验上受到质疑,使离子冲击器不确定.
研究的目的:
- 为了确定分泌颗粒中的离子短路导电的分子同一性.
- 调查染色素B (CHGB) 在分泌颗粒功能中的作用.
- 确定CHGB对神经内分泌细胞成熟和信号传递的影响.
主要方法:
- 在培养和初级神经内分泌细胞中测量细粒体内pH值.
- 货物成熟测定,包括亲胰岛素-胰岛素转换和多巴胺负载.
- 在Chgb-/-小鼠中的基因操纵和初级β细胞的分析.
- 使用删除突变体和测试其他离子通道候选物的功能研究 (CLC-3/5,ANO-1/2).
主要成果:
- 染色素B (CHGB) 被确定为分泌颗粒离子冲击器的核心组成部分.
- 功能性的CHGB+通道对于正常的颗粒酸性化,亲胰岛素-胰岛素转化和多巴胺负载至关重要.
- Chgb-/-小鼠表现出颗粒脱酸,胰岛素分泌发生变化和单胺含量降低.
- 其他离子通道候选物 (CLC-3/5,ANO-1/2) 被排除在外.
结论:
- CHGB+通道是长期以来在分泌颗粒中寻求的离子分离器.
- 在神经内分泌细胞中,CHGB功能对于调节的分泌和颗粒成熟至关重要.
- 在脊椎动物中,CHGB+通道得到保护,在受调节的分泌通路中起着至关重要的作用.
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