Structural requirements for PACSIN/Syndapin operation during zebrafish embryonic notochord development.
Structural requirements for PACSIN/Syndapin operation during zebrafish embryonic notochord development.
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DOI：
10.1371/journal.pone.0008150
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发表时间：
2009-12-03
期刊：
影响因子：
3.7
通讯作者：
Traub LM
中科院分区：
文献类型：
--
作者：
Edeling MA;Sanker S;Shima T;Umasankar PK;Höning S;Kim HY;Davidson LA;Watkins SC;Tsang M;Owen DJ;Traub LM
PACSIN/Syndapin蛋白是参与内吞作用的膜活性支架。果蝇Syndapin N-末端EFC结构域的结构揭示了一个新月形的反平行二聚体，其对磷酸肌醇具有高亲和力，并且在凹面上具有独特的膜插入叉。结合斑马鱼的结构，生化和反向遗传方法定义了一个重要的作用Syndapin的直系同源物，Pacsin 3，在胚胎发育过程中的脊索的早期形成。在pacsin 3-morphant胚胎中，脊索前体的中线会聚是有缺陷的，因为轴向中胚层细胞不能正确地生长、迁移和分化。pacsin 3 morphant表型的发育不良的身体轴和扭曲的躯干被救出的果蝇Syndapin的异位表达，并严重依赖于从弓状Syndapin EFC域的表面突出的叉和能力的反平行二聚体紧密结合到磷酸肌醇。我们的数据证实了定向迁移，胞吞作用和细胞规格之间的联系在胚胎形态发生和突出的Pacsin 3在这种耦合在脊索中的关键作用。
PACSIN/Syndapin proteins are membrane-active scaffolds that participate in endocytosis. The structure of the Drosophila Syndapin N-terminal EFC domain reveals a crescent shaped antiparallel dimer with a high affinity for phosphoinositides and a unique membrane-inserting prong upon the concave surface. Combined structural, biochemical and reverse genetic approaches in zebrafish define an important role for Syndapin orthologue, Pacsin3, in the early formation of the notochord during embryonic development. In pacsin3-morphant embryos, midline convergence of notochord precursors is defective as axial mesodermal cells fail to polarize, migrate and differentiate properly. The pacsin3 morphant phenotype of a stunted body axis and contorted trunk is rescued by ectopic expression of Drosophila Syndapin, and depends critically on both the prong that protrudes from the surface of the bowed Syndapin EFC domain and the ability of the antiparallel dimer to bind tightly to phosphoinositides. Our data confirm linkage between directional migration, endocytosis and cell specification during embryonic morphogenesis and highlight a key role for Pacsin3 in this coupling in the notochord.
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DOI：
10.1107/s0907444905036693
发表时间：
2006-01-01
影响因子：
2.2
作者：
Evans, P
通讯作者：
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DOI：
10.1107/s0907444904019158
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影响因子：
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影响因子：
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影响因子：
25
作者：
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DOI：
10.1523/jneurosci.1976-09.2009
发表时间：
2009-06-17
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
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作者：
Clayton EL;Anggono V;Smillie KJ;Chau N;Robinson PJ;Cousin MA
通讯作者：
Cousin MA