Department of Physiology and Biophysics, University of Miami School of Medicine, FL, USA.
FEBS Lett. 2018 Oct;592(19):3201-3209. doi: 10.1002/1873-3468.13115. Epub 2018 Jun 5.
The Pannexin1 (Panx1) membrane channel responds to different stimuli with distinct channel conformations. Most stimuli induce a large cation- and ATP-permeable conformation, hence Panx1 is involved in many physiological processes entailing purinergic signaling. For example, oxygen delivery in the peripheral circulatory system is regulated by ATP released from red blood cells and endothelial cells through Panx1 channels. The same membrane channel, however, when stimulated by positive membrane potential or by cleavage with caspase 3, is highly selective for the passage of chloride ions, excluding cations and ATP. Although biophysical data do not allow a distinction between the chloride-selective channels induced by voltage or by caspase cleavage, there must be other subtle differences in the structure, because overexpression of wtPanx1 is well tolerated by cells, while expression of the truncation mutant Panx1Δ378 results in slow cell death. Thus, in addition to the well-characterized two open conformations, there might be a third, more subtle conformational change involved in cell death.
质膜通道蛋白 Pannexin1（Panx1）对不同刺激的反应具有不同的通道构象。大多数刺激诱导产生大的阳离子和 ATP 可通透的构象，因此 Panx1 参与涉及嘌呤能信号转导的许多生理过程。例如，外周循环系统中的氧输送受红细胞和内皮细胞通过 Panx1 通道释放的 ATP 调节。然而，当该膜通道受到正膜电位或 caspase 3 切割的刺激时，对氯离子的通透性非常高，排斥阳离子和 ATP。尽管生物物理数据不允许区分电压或半胱天冬酶切割诱导的氯离子选择性通道，但在结构上肯定存在其他细微差异，因为 wtPanx1 的过表达被细胞很好地耐受，而截断突变体 Panx1Δ378 的表达导致细胞死亡缓慢。因此，除了特征明确的两种开放构象外，可能还存在涉及细胞死亡的第三种更细微的构象变化。
