论文部分内容阅读
电压门控Ca2+通道是由多个亚基组成的膜蛋白,其分布广泛,生理功能极为重要,可被众多蛋白和信号传导通路调节。本综述重点介绍蛋白质水解对电压门控Ca2+通道的调节作用及其生理功能。Ca2+通道的主亚基Cavα1可被蛋白质水解,从而调控Ca2+通道的功能和降解,影响基因表达和细胞兴奋性。根据其组织分布,l类Ca2+通道有两种水解模式:在心脏和骨骼肌,Cavα1的羧基末端被水解后与剩余的羧基端结合,抑制Ca2+通道电流。这种自身抑制可被体内分泌的肾上腺素解除,引发心肌和骨骼肌Ca2+电流大量增加,在“打或逃”之类的应激反应中起重要作用,Cavα1羧基末端水解在大脑也存在,并可能是由calpain蛋白质水解酶催化;在某些大脑区域,Cavα1的整个羧基端可被水解并迁移至细胞核,起到转录因子的作用。P/Q类Ca2+通道Cavα1的羧基末端也可被水解,并迁移到细胞核。许多基因突变产生截断型P/QCavα1,而这些截断型Cavα1可严重影响正常Ca2+通道的功能,导致人类的疾病。截断型N类Ca2+通道Cavα1可通过诱变产生,影响正常通道的表达。新型Ca2+通道水解新模式可能是未来Ca2+通道研究中一个重要的探索方向。
The voltage-gated Ca2 + channel is a membrane protein composed of multiple subunits that is widely distributed and of vital physiological function and is regulated by numerous proteins and signaling pathways. This review highlights the regulatory role of proteolysis on voltage-gated Ca2 + channels and their physiological functions. Cavα1, a major subunit of Ca2 + channels, can be proteolyzed to regulate the function and degradation of Ca2 + channels and affect gene expression and cell excitability. Based on their histological distribution, there are two modes of hydrolysis for the class I Ca2 + channels: In the heart and skeletal muscle, the carboxyl terminal of Caval is hydrolyzed and binds to the remaining carboxyterminals, inhibiting Ca2 + channel currents. This self-inhibition can be excreted by the body’s release of epinephrine, triggering a significant increase in myocardial and skeletal muscle Ca2 + currents, playing an important role in stress responses such as “fight or run”, Caval carboxy-terminal hydrolysis also exists in the brain , And may be catalyzed by the calpain proteolytic enzyme; in some brain regions, the entire carboxy-terminus of Caval may be hydrolyzed and migrate to the nucleus, acting as a transcription factor. The carboxy terminal end of Caval, a P / Q-type Ca2 + channel, can also be hydrolyzed and migrate to the nucleus. Many gene mutations produce truncated P / QCavα1, and these truncated Cavα1 can seriously affect the normal Ca2 + channel function, leading to human disease. Truncated type N Ca2 + channel Caval can be generated by mutagenesis, affecting normal channel expression. The new Ca2 + channel hydrolysis new mode may be an important exploration direction in the future Ca2 + channel study.