Spatial regulation of membrane fusion controlled by modification of phosphoinositides.
Spatial regulation of membrane fusion controlled by modification of phosphoinositides.
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DOI：
10.1371/journal.pone.0012208
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发表时间：
2010-08-17
期刊：
影响因子：
3.7
通讯作者：
Larijani B
中科院分区：
文献类型：
--
作者：
Dumas F;Byrne RD;Vincent B;Hobday TM;Poccia DL;Larijani B
膜融合在从囊泡运输到有丝分裂时核膜重建的许多细胞过程中起着核心作用，但天然膜融合的基础机制还不清楚。合成膜的研究和理论考虑表明，以负曲率为特征的脂质（如二酰基甘油（DAG））的积累促进融合。然而，脂质在天然膜的膜融合中的具体作用还没有很好地建立。核膜（NE）组件被用作膜融合的模型。已经分离出高度富集产生DAG所需的酶和底物的天然膜群体，并且所述天然膜群体是导致核膜形成的融合所需的，尽管其仅贡献少量最终并入NE中的膜。它被假定为启动和调节膜融合。在这里，我们使用一个多学科的方法，包括亚细胞膜纯化，荧光光谱和福斯特共振能量转移（FRET）/双光子荧光寿命成像显微镜（FLIM），以证明囊泡融合的启动产生于两个独特的网站，这些囊泡结合到染色质。融合随后传播到内质网衍生的膜，其构成NE的大部分以最终包围染色质。我们展示了如何启动多囊泡融合可以控制本地化生产的DAG和双向传播。后一过程需要磷脂酶C（PLCγ）、GTP水解和（磷脂酰肌醇-（4，5）-二磷酸）（PtdIns（4，5）P2）。我们讨论了膜融合调节和空间控制利用这样的机制的一般影响。
Membrane fusion plays a central role in many cell processes from vesicular transport to nuclear envelope reconstitution at mitosis but the mechanisms that underlie fusion of natural membranes are not well understood. Studies with synthetic membranes and theoretical considerations indicate that accumulation of lipids characterised by negative curvature such as diacylglycerol (DAG) facilitate fusion. However, the specific role of lipids in membrane fusion of natural membranes is not well established. Nuclear envelope (NE) assembly was used as a model for membrane fusion. A natural membrane population highly enriched in the enzyme and substrate needed to produce DAG has been isolated and is required for fusions leading to nuclear envelope formation, although it contributes only a small amount of the membrane eventually incorporated into the NE. It was postulated to initiate and regulate membrane fusion. Here we use a multidisciplinary approach including subcellular membrane purification, fluorescence spectroscopy and Förster resonance energy transfer (FRET)/two-photon fluorescence lifetime imaging microscopy (FLIM) to demonstrate that initiation of vesicle fusion arises from two unique sites where these vesicles bind to chromatin. Fusion is subsequently propagated to the endoplasmic reticulum-derived membranes that make up the bulk of the NE to ultimately enclose the chromatin. We show how initiation of multiple vesicle fusions can be controlled by localised production of DAG and propagated bidirectionally. Phospholipase C (PLCγ), GTP hydrolysis and (phosphatidylinsositol-(4,5)-bisphosphate (PtdIns(4,5)P2) are required for the latter process. We discuss the general implications of membrane fusion regulation and spatial control utilising such a mechanism.
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影响因子：
4.8
作者：
Barona, T;Byrne, RD;Poccia, DL
通讯作者：
Poccia, DL
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4.1
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