Endocytosis and endosomes at the crossroads of regulating trafficking of axon outgrowth-modifying receptors.
Endocytosis and endosomes at the crossroads of regulating trafficking of axon outgrowth-modifying receptors.
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DOI：
10.1111/j.1600-0854.2011.01213.x
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发表时间：
2011-09
期刊：
影响因子：
--
通讯作者：
Yap CC
中科院分区：
文献类型：
--
作者：
Winckler B;Yap CC
在神经元中，许多受体必须正确定位到轴突或树突才能发挥正常功能。在发育过程中，神经生长和引导的受体靶向轴突并定位于生长锥，其中配体激活受体导致轴突生长的促进或抑制。配体结合下游的信号转导结果由神经元质膜上受体的位置、水平和停留时间决定。因此，控制这些受体运输的机制对于电路的正确布线至关重要。膜蛋白通过多种途径在轴突表面积累，包括跨高尔基体网络中的极化分选、内体中的分选以及通过内吞作用去除。内体还在生长促进和抑制分子的信号传导途径中发挥重要作用：源自内吞作用的信号传导内体对于从生长锥到细胞体的信号传导非常重要。促进生长的神经营养因子和抑制生长的 Nogo-A 可以在生长锥处利用 EHD4/pincher 依赖性内吞作用来实现各自的逆行信号传导。除了内体的逆行运输之外，几种受体也发生内体中轴突的顺行运输，包括轴突生长促进细胞粘附分子 L1/NgCAM 和 TrkA。 L1/NgCAM 的轴突极化还依赖于 EHD4/pincher 依赖性内吞作用。在这篇综述中，我们将重点关注据报道其运输受到内体调节因子 EHD4/pincher 家族调节的受体，即 L1/NgCAM、Trk 和 Nogo-A。我们将首先总结这些蛋白质轴突运输的潜在途径，然后讨论 EHD4/pincher 在介导其内吞作用中的潜在作用。
In neurons, many receptors must be localized correctly to axons or dendrites for proper function. During development, receptors for nerve growth and guidance are targeted to axons and localized to growth cones where receptor activation by ligands results in promotion or inhibition of axon growth. Signaling outcomes downstream of ligand binding are determined by the location, levels, and residence times of receptors on the neuronal plasma membrane. Therefore, the mechanisms controlling the trafficking of these receptors are crucial to the proper wiring of circuits. Membrane proteins accumulate on the axonal surface by multiple routes, including polarized sorting in the trans-Golgi network, sorting in endosomes, and removal by endocytosis. Endosomes also play important roles in the signaling pathways for both growth-promoting and -inhibiting molecules: signaling endosomes derived from endocytosis are important for signaling from growth cones to cell bodies. Growth-promoting neurotrophins and growth-inhibiting Nogo-A can use EHD4/pincher-dependent endocytosis at the growth cone for their respective retrograde signaling. In addition to retrograde transport of endosomes, anterograde transport to axons in endosomes also occurs for several receptors, including the axon-outgrowth promoting cell adhesion molecule L1/NgCAM and TrkA. L1/NgCAM also depends on EHD4/pincher-dependent endocytosis for its axonal polarization. In this review, we will focus on receptors whose trafficking has been reported to be modulated by the EHD4/pincher family of endosomal regulators, namely L1/NgCAM, Trk and Nogo-A. We will first summarize the pathways underlying the axonal transport of these proteins and then discuss the potential roles of EHD4/pincher in mediating their endocytosis.
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DOI：
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发表时间：
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期刊：
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影响因子：
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发表时间：
1988-02
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