Kawai Takafumi, Okamura Yasushi
Integrative Physiology Program, Graduate School of Medicine, Osaka University, Suita, Japan.
Graduate School of Frontier Bioscience, Osaka University, Suita, Japan.
Front Physiol. 2022 Feb 7;13:834180. doi: 10.3389/fphys.2022.834180. eCollection 2022.
The previous studies revealed that many types of ion channels have sensitivity to PtdIns(4,5)P, which has been mainly shown using heterologous expression system. On the other hand, there remains few evidence showing that PtdIns(4,5)P natively regulate the ion channel activities in physiological context. Our group recently discovered that a sperm specific K channel, Slo3, is natively regulated by PtdIns(4,5)P in sperm flagellum. Very interestingly, a principal piece, to which Slo3 specifically localized, had extremely low density of PtdIns(4,5)P compared to the regular cell plasma membrane. Furthermore, our studies and the previous ones also revealed that Slo3 had much stronger PtdIns(4,5)P affinity than KCNQ2/3 channels, which are widely regulated by endogenous PtdIns(4,5)P in neurons. Thus, the high-PtdIns(4,5)P affinity of Slo3 is well-adapted to the specialized PtdIns(4,5)P environment in the principal piece. This study sheds light on the relationship between PtdIns(4,5)P-affinity of ion channels and their PtdIns(4,5)P environment in native cells. We discuss the current understanding about PtdIns(4,5)P affinity of diverse ion channels and their possible regulatory mechanism in native cellular environment.
先前的研究表明，许多类型的离子通道对磷脂酰肌醇-4,5-二磷酸（PtdIns(4,5)P）具有敏感性，这主要是在异源表达系统中得到证实。另一方面，几乎没有证据表明PtdIns(4,5)P在生理环境中对离子通道活性具有天然调节作用。我们小组最近发现，一种精子特异性钾通道Slo3在精子鞭毛中受到PtdIns(4,5)P的天然调节。非常有趣的是，与正常细胞膜相比，Slo3特异性定位的主段中PtdIns(4,5)P的密度极低。此外，我们的研究以及之前的研究还表明，Slo3对PtdIns(4,5)P的亲和力比KCNQ2/3通道强得多，而KCNQ2/3通道在神经元中受到内源性PtdIns(4,5)P的广泛调节。因此，Slo3对PtdIns(4,5)P的高亲和力非常适合主段中特殊的PtdIns(4,5)P环境。这项研究揭示了离子通道的PtdIns(4,5)P亲和力与其在天然细胞中的PtdIns(4,5)P环境之间的关系。我们讨论了目前对不同离子通道的PtdIns(4,5)P亲和力及其在天然细胞环境中可能的调节机制的理解。
