内膜系统由生物合成途径中的细胞器膜组成:内质网(ER),高尔基体,和分泌囊泡,以及降解途径中的那些:早期内体,macropinosomes,吞噬体,自噬体,晚期内体,和溶酶体.这些内膜细胞器/囊泡一起合成,修改,包,运输,降解蛋白质,碳水化合物,和脂质,调节细胞合成代谢和分解代谢之间的平衡。内膜上存在较大的离子浓度梯度-大多数内膜细胞器的Ca2梯度和酸性隔室的H梯度。离子(Na+,K+,H+,Ca2+,和Cl-)通道在细胞层膜上控制响应细胞线索的离子通量,允许细胞溶胶和细胞器腔之间的快速信息交换。细胞器蛋白质组学的最新进展,细胞器电生理学,腔和近层离子成像已导致大约二十个膜内离子通道的分子鉴定和功能表征。例如,而IP3R1-3通道介导Ca2+从ER释放响应神经递质和激素刺激,TRPML1-3和TMEM175通道介导溶酶体Ca2+和H+释放,分别,以回应营养和贩运线索。这篇综述旨在总结目前对这些内膜通道的理解,专注于它们的亚细胞定位,离子渗透性能,门控机制,细胞生物学功能,和疾病的相关性。
The endomembrane system consists of organellar membranes in the biosynthetic pathway [endoplasmic reticulum (ER), Golgi apparatus, and secretory vesicles] as well as those in the degradative pathway (early endosomes, macropinosomes, phagosomes, autophagosomes, late endosomes, and lysosomes). These endomembrane organelles/vesicles work together to synthesize, modify, package, transport, and degrade proteins, carbohydrates, and lipids, regulating the balance between cellular anabolism and catabolism. Large ion concentration gradients exist across endomembranes: Ca2+ gradients for most endomembrane organelles and H+ gradients for the acidic compartments. Ion (Na+, K+, H+, Ca2+, and Cl-) channels on the organellar membranes control ion flux in response to cellular cues, allowing rapid informational exchange between the cytosol and organelle lumen. Recent advances in organelle proteomics, organellar electrophysiology, and luminal and juxtaorganellar ion imaging have led to molecular identification and functional characterization of about two dozen endomembrane ion channels. For example, whereas IP3R1-3 channels mediate Ca2+ release from the ER in response to neurotransmitter and hormone stimulation, TRPML1-3 and TMEM175 channels mediate lysosomal Ca2+ and H+ release, respectively, in response to nutritional and trafficking cues. This review aims to summarize the current understanding of these endomembrane channels, with a focus on their subcellular localizations, ion permeation properties, gating mechanisms, cell biological functions, and disease relevance.