Processing-dependent trafficking of Sonic hedgehog to the regulated secretory pathway in neurons
Processing-dependent trafficking of Sonic hedgehog to the regulated secretory pathway in neurons
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DOI：
10.1016/j.mcn.2010.12.009
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发表时间：
2011-03-01
影响因子：
3.5
通讯作者：
Wallace, Valerie A.
中科院分区：
文献类型：
--
作者：
Beug, Shawn T.;Parks, Robin J.;Wallace, Valerie A.
神经元是分泌形态原Sonic hedgehog（Shh）的重要来源，然而，关于Shh的运输和分泌的神经元特异性调节知之甚少。为了研究这一过程，我们研究了亚细胞分布的Shh在原代神经元和分化的神经内分泌细胞系的细胞通过荧光显微镜和生化分级。在视网膜神经节细胞中，内源性Shh以细胞内和细胞外点状分布于索马、树突、轴突和轴突终末。Shh（+）点双向移动，并与突触小泡（SV）和致密核心颗粒的标记物共定位。脂质修饰和蛋白水解需要Shh分选到SV和细胞表面缔合。最后，与其与调节分泌囊泡的关联一致，Shh分泌可以在去极化条件下诱导。两者合计，这些观察结果表明，长距离Shh运输和信号在神经元中涉及运输到调节分泌途径和细胞表面积累的Shh轴突，并表明神经元活动和Shh释放之间的联系。(C)2010年爱思唯尔公司All rights reserved.
Neurons are an important source of the secreted morphogen Sonic hedgehog (Shh), however, little is known about neuron-specific regulation of Shh transport and secretion. To study this process, we investigated the subcellular distribution of Shh in primary neurons and differentiated cells of a neuroendocrine cell line by fluorescence microscopy and biochemical fractionation. In retinal ganglion cells, endogenous Shh was distributed as intra- and extracellular puncta at the soma, dendrites, axons and neurite terminals. Shh(+) puncta move bidirectionally and colocalize with markers of synaptic vesicles (SVs) and dense core granules. Lipid modification and proteolysis were required for Shh sorting to SVs and cell surface association. Finally, consistent with its association with regulated secretory vesicles, Shh secretion could be induced under depolarizing conditions. Taken together, these observations suggest that long-range Shh transport and signalling in neurons involves trafficking to the regulated secretory pathway and cell surface accumulation of Shh on axons and suggests a link between neuronal activity and Shh release. (C) 2010 Elsevier Inc. All rights reserved.