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一个工程贩运生物传感器揭示了DNAJC13在DOR下调调节中的作用

Brandon Novy¹, Aleksandra Dagunts¹, Tatum Weishaar¹

¹Department of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, OR, USA.

Nature chemical biology

|September 2, 2024

概括

研究人员使用新型生物传感器确定了控制G蛋白结合受体 (GPCR) 贩运的新基因. 发现DNAJC13通过内体-溶酶体通路调节GPCR运输,影响受体恒温.

科学领域:

细胞生物学细胞生物学
分子药理学分子药理学
基因组学就是基因组学.

背景情况:

通过内体-溶酶体通路的G蛋白结合受体 (GPCR) 贩运对于细胞平衡至关重要.
鉴定调节GPCR贩运的基因是复杂的,因为细胞分类机制的复杂性.

研究的目的:

开发一种敏感的生物传感器,用于监测GPCR表达和溶酶体贩运.
进行全基因组选,以确定参与 δ-阿片类受体 (DOR) 调节的新基因.

主要方法:

开发一种高灵敏度的生物传感器,将工程化过氧化酶APEX2与基质Amplex UltraRed (AUR) 结合起来,用于GPCR-lysosomal贩运.
全基因组的CRISPR干扰 (CRISPRi) 屏幕用于识别调节DOR表达和贩运的基因.

主要成果:

鉴定了492个基因,包括已知和新型调节器,影响DOR功能.
发现DNAJC13作为一种新型调节剂,可以控制多个GPCR的贩运,包括DOR.
证明DNAJC13调节内体蛋白质组合和稳态,从而影响GPCR贩运.

结论:

新的GPCR-APEX2 / AUR生物传感器测定对于大规模的GPCR贩运遗传查是有效的.
DNAJC13在GPCR内体-解体体贩运和恒温中发挥着重要作用.
这项研究扩大了对控制GPCR贩运和细胞信号传输的遗传调节者的理解.

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