Insights into the mechanisms of membrane curvature and vesicle scission by the small GTPase Sar1 in the early secretory pathway.

Insights into the mechanisms of membrane curvature and vesicle scission by the small GTPase Sar1 in the early secretory pathway.
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DOI:
10.1016/j.jmb.2014.08.023
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发表时间:
2014-11-11
影响因子:
5.6
通讯作者:
Stagg, Scott M.
Stagg, Scott M.
中科院分区:
生物学2区
文献类型:
--
作者:
Hariri, Hanaa;Bhattacharya, Nilakshee;Johnson, Kerri;Noble, Alex J.;Stagg, Scott M.

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已知小 GTP 酶蛋白 Sar1 参与 COPII 包被囊泡形成的启动和新生囊泡从 ER 的分裂。 Sar1 膜重塑机制的分子细节仍未解决。在这里,我们展示了 Sar1 将合成脂质体转化为不同形态的结构,包括小管和分离的囊泡。我们证明,Sar1 单独能够以取决于占据膜的 Sar1 分子浓度的方式进行囊泡分裂。 Sar1 分子在低曲率膜上排列形成延伸的晶格。当曲率局部增加时,该晶格的连续性就会被破坏。构成有序晶格的最小重复单元是Sar1二聚体。通过用直径均匀的半乳糖神经酰胺脂管代替球形脂质体,重建了 Sar1 晶格的三维结构。这些数据表明 Sar1 二聚化是收缩膜曲率形成的原因。我们提出了一个模型,通过该模型,Sar1 二聚体组装成有序阵列,以促进膜收缩和 COPII 引导的囊泡分裂。
The small GTPase protein Sar1 is known to be involved in both the initiation of COPII coated vesicle formation and scission of the nascent vesicle from the ER. The molecular details for the mechanism of membrane remodeling by Sar1 remain unresolved. Here we show that Sar1 transforms synthetic liposomes into structures of different morphologies including tubules and detached vesicles. We demonstrate that Sar1 alone is competent for vesicle scission in a manner that depends on the concentration of Sar1 molecules occupying the membrane. Sar1 molecules align on low curvature membranes to form an extended lattice. The continuity of this lattice breaks down as the curvature locally increases. The smallest repeating unit constituting the ordered lattice is a Sar1 dimer. The three dimensional structure of the Sar1 lattice was reconstructed by substituting spherical liposomes with galactoceramide lipid tubules of homogeneous diameter. These data suggest that Sar1 dimerization is responsible for the formation of constrictive membrane curvature. We propose a model whereby Sar1 dimers assemble into ordered arrays to promote membrane constriction and COPII-directed vesicle scission.
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