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A 14-3-3γ 3 dimer-based scaffold bridges CtBP1-S/BARS to PI(4)KIIIβ 2 to regulate post-Golgi carrier formation

机译:一个基于14-3-3γ3二聚体的支架将CtBP1-S / BARS桥接至PI(4)KIIIβ2以调节高尔基体后载体的形成

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摘要

Large pleiomorphic carriers leave the Golgi complex for the plasma membrane by en bloc extrusion of specialized tubular domains, which then undergo fission. Several components of the underlying molecular machinery have been identified, including those involved in the budding/initiation of tubular carrier precursors (for example, the phosphoinositide kinase PI(4)KIIIβ 2, the GTPase ARF, and FAPP2), and in the fission of these precursors (for example, PKD, CtBP1-S/BARS). However, how these proteins interact to bring about carrier formation is poorly understood. Here, we describe a protein complex that mediates carrier formation and contains budding and fission molecules, as well as other molecules, such as the adaptor protein 14-3-3γ3. Specifically, we show that 14-3-3γ 3 dimers bridge CtBP1-S/BARS with PI(4)KIIIβ 2, and that the resulting complex is stabilized by phosphorylation by PKD and PAK. Disrupting the association of these proteins inhibits the fission of elongating carrier precursors, indicating that this complex couples the carrier budding and fission processes.
机译:大的多晶型载体通过整体挤出特殊的管状结构域而离开高尔基复合体,进入质膜,然后发生裂变。已经确定了潜在分子机制的几个组成部分,包括那些参与管状载体前体的萌芽/初始化的组成部分(例如,磷酸肌醇激酶PI(4)KIIIβ2,GTPase ARF和FAPP2)以及这些前体(例如PKD,CtBP1-S / BARS)。然而,人们对这些蛋白质如何相互作用以导致载体形成的了解很少。在这里,我们描述了一种蛋白质复合物,它介导载体的形成,并包含出芽和裂变分子,以及其他分子,例如衔接蛋白14-3-3γ3。具体来说,我们表明14-3-3γ3二聚体桥接CtBP1-S / BARS与PI(4)KIIIβ2,并且所得复合物通过PKD和PAK磷酸化而稳定。破坏这些蛋白质的缔合会抑制延长的载体前体的裂变,表明该复合物将载体的出芽和裂变过程结合在一起。

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