Graduate Program in Molecular Science, Ryerson University, Toronto, ON, Canada M5B2K3.
Department of Chemistry and Biology, Ryerson University, Toronto, ON, Canada M5B2K3.
Bioessays. 2017 Dec;39(12). doi: 10.1002/bies.201700121. Epub 2017 Oct 4.
Phosphoinositides (PtdInsPs) modulate a plethora of functions including signal transduction and membrane trafficking. PtdInsPs are thought to consist of seven interconvertible species that localize to a specific organelle, to which they recruit a set of cognate effector proteins. Here, in reviewing the literature, we argue that this model needs revision. First, PtdInsPs can carry a variety of acyl chains, greatly boosting their molecular diversity. Second, PtdInsPs are more promiscuous in their localization than is usually acknowledged. Third, PtdInsP interconversion is likely achieved through kinase-phosphatase enzyme complexes that coordinate their activities and channel substrates without affecting bulk substrate population. Additionally, we contend that despite hundreds of PtdInsP effectors, our attention is biased toward few proteins. Lastly, we recognize that PtdInsPs can act to nucleate coincidence detection at the effector level, as in PDK1 and Akt. Overall, better integrated models of PtdInsP regulation and function are not only possible but needed.
磷脂酰肌醇磷酸（PtdInsPs）调节多种功能，包括信号转导和膜运输。人们认为 PtdInsPs 由七种可相互转化的物种组成，这些物种定位于特定的细胞器，向其募集一组同源效应蛋白。在这里，我们在回顾文献时认为，这种模式需要修改。首先，PtdInsPs 可以携带多种酰基链，大大提高了其分子多样性。其次，PtdInsPs 的定位比通常承认的更为混杂。第三，PtdInsP 的相互转化可能是通过激酶-磷酸酶酶复合物实现的，这些复合物协调它们的活性并引导底物，而不影响大量底物群体。此外，我们认为，尽管有数百种 PtdInsP 效应物，但我们的注意力偏向少数几种蛋白质。最后，我们认识到 PtdInsPs 可以在效应物水平上起核作用，如 PDK1 和 Akt。总的来说，更好的 PtdInsP 调节和功能的综合模型不仅是可能的，而且是必要的。
