Multivalent Cation-Bridged PI(4,5)P2 Clusters Form at Very Low Concentrations.
Multivalent Cation-Bridged PI(4,5)P2 Clusters Form at Very Low Concentrations.
复制标题
多价阳离子桥接 PI(4,5)P2 簇在极低浓度下形成。
DOI：
10.1016/j.bpj.2018.04.048
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发表时间：
2018
影响因子：
3.4
通讯作者：
Feigenson,GeraldW
中科院分区：
文献类型：
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作者：
Wen,Yi;Vogt,VolkerM;Feigenson,GeraldW
磷脂酰肌醇4，5-二磷酸（PI（4，5）P2或PIP 2）是真核细胞质膜内叶的关键组分。据报道，在模型膜中，PIP 2形成簇，但这些局部不同的条件是否会产生不同的未簇集和簇集的PIP 2池尚不清楚。通过使用荧光自猝灭和Förster共振能量转移测定，我们发现PIP 2在低于总脂质的0.05 mol%的非常低的浓度下自缔合。这些簇的形成依赖于生理二价金属离子，如Ca 2+，Mg 2+，Zn 2+，或三价离子Fe 3+和Al 3+。PIP 2簇的形成也是头基特异性的，在很大程度上独立于酰基链的类型。同样标记的磷脂磷脂酰胆碱，磷脂酰乙醇胺，磷脂酰丝氨酸，磷脂酰肌醇没有表现出这样的集群。然而，6种磷脂酰肌醇与PIP 2共聚。PIP 2阳离子聚集的程度受到周围脂质组成的显著影响，胆固醇和磷脂酰肌醇增强了这种行为。我们建议，PIP 2阳离子桥接簇的形成，这可能是类似于胶束的形成，可以被用来作为一个物理模型，什么可能是不同的池PIP 2在生物膜。据我们所知，这项研究提供了PIP 2在如此低的浓度下形成簇的第一个证据。据我们所知，PIP 2在模型膜中以如此极低的浓度形成这种簇的性质揭示了PIP 2在细胞中可能发生的新行为，其中局部多价金属离子、脂质组合物和各种结合蛋白可以极大地影响PIP 2的性质。反过来，这些不同的PIP 2库可以进一步调节细胞事件。
Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2or PIP2), is a key component of the inner leaflet of the plasma membrane in eukaryotic cells. In model membranes, PIP2 has been reported to form clusters, but whether these locally different conditions could give rise to distinct pools of unclustered and clustered PIP2 is unclear. By use of both fluorescence self-quenching and Förster resonance energy transfer assays, we have discovered that PIP2 self-associates at remarkably low concentrations starting below 0.05 mol% of total lipids. Formation of these clusters was dependent on physiological divalent metal ions, such as Ca2+, Mg2+, Zn2+, or trivalent ions Fe3+and Al3+. Formation of PIP2 clusters was also headgroup-specific, being largely independent of the type of acyl chain. The similarly labeled phospholipids phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol exhibited no such clustering. However, six phosphoinositide species coclustered with PIP2. The degree of PIP2 cation clustering was significantly influenced by the composition of the surrounding lipids, with cholesterol and phosphatidylinositol enhancing this behavior. We propose that PIP2 cation-bridged cluster formation, which might be similar to micelle formation, can be used as a physical model for what could be distinct pools of PIP2 in biological membranes. To our knowledge, this study provides the first evidence of PIP2 forming clusters at such low concentrations. The property of PIP2 to form such clusters at such extremely low concentrations in model membranes reveals, to our knowledge, a new behavior of PIP2 proposed to occur in cells, in which local multivalent metal ions, lipid compositions, and various binding proteins could greatly influence PIP2 properties. In turn, these different pools of PIP2 could further regulate cellular events.