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腾讯登录Sci Signal：星形胶质细胞新作用
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星形胶质细胞(astrocyte)之前被认为是神经元的辅助性细胞，如今研究人员发现它们自己能够给发送化学信号而不是电信号。它们将这些化学信号发送给神经元、血管细胞和其他星形胶质细胞来改善突触信号传送效率。日本理化研究所脑科学研究院研究员Katsuhiko Mikoshiba和Hiroko Bannai领导的一个研究小组描述了允许星形胶质细胞给它们网络中的每个细胞发送信号的机制。
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星形胶质细胞拥有一个位于中间的胞体(soma)和许多个射线状臂(ray-like arm)，而且这些射线状臂连接到它们调节的细胞上。健康的星形胶质细胞通过每个射线状臂发送相互独立的钙离子信号。已知这些信号受到细胞膜中一种被称作代谢型谷氨酸受体(metabotropic glutamate receptor, mGluR5)的受体的调节，但是科学家们不清楚的是如何将这些信号分解为单个钙离子信号。理解这种特异性可能在治疗上具有重要意义，这是因为在受到阿尔茨海默病或癫痫症影响的大脑中，星形胶质细胞发送全局性信号，打个比方而言，这种全局性信号更像是扩音器广播，而健康星形胶质细胞发送的信号类似于电话呼叫。
为了理解星形胶质细胞信号如何受到调节，研究人员对单个mGluR5受体进行量子点---当激发时能够发光的半导体纳米晶体---标记，然后观察这些受体如何穿过细胞膜。视频画面揭示mGluR5受体并不从射线状臂到达胞体。在正常星形胶质细胞中，mGluR5选择性扩散屏障能够通过钙离子信号区室化来允许每个射线状臂独立地调节它的接触伙伴。
为了研究这种扩散屏障的特征，Mikoshiba研究团队试图破坏它。过度表达的mGluR5覆盖着这种扩散屏障，据此，他们推断这种屏障是由与mGluR5胞质部分相互作用的蛋白组成的。每个屏障蛋白与单个mGluR5分子配对，从而阻止它跨到胞体中。然而，屏障蛋白的数量是有限的，过量的mGluR5让一些受体能够自由地跨进胞体，因而能够让全局性信号通过星形胶质细胞中的每个射线状臂。
阿尔茨海默病和癫痫症实验性动物模型证实星形胶质细胞拥有高浓度的mGlu5分子。研究人员相信理解这种扩散屏障的分子特征将有助于人们找到用于治疗这些疾病的新靶标。一旦揭示出这种屏障的分子特征，他们希望构建出一种缺乏星形胶质细胞屏障蛋白的转基因小鼠。Mikoshiba说，“我们非常吃惊地了解到全局性星形胶质细胞钙离子信号对神经元网络和神经-血管耦合(neuro-vascular coupling)的影响。”
本文编译自<a href="http://medicalxpress.com/news/2012-08-starring-role-astrocytes.html" target="_blank">A new starring role for astrocytes</a>
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<img src="http://www.bioon.com/biology/UploadFiles/201208/2012081201392808.gif" alt="" width="113" height="149" border="0" />
<a title="" href="http://dx.doi.org/10.1126/scisignal.2002498" target="_blank">doi: 10.1126/scisignal.2002498</a>
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<br/><strong>Receptor-Selective Diffusion Barrier Enhances Sensitivity of Astrocytic Processes to Metabotropic Glutamate Receptor Stimulation</strong><br/>
Misa Arizono1,2, Hiroko Bannai1*, Kyoko Nakamura3,4, Fumihiro Niwa1,5, Masahiro Enomoto1, Toru Matsu-ura1, Akitoshi Miyamoto1,2, Mark W. Sherwood1, Takeshi Nakamura3, and Katsuhiko Mikoshiba
Metabotropic glutamate receptor (mGluR)–dependent calcium ion (Ca2+) signaling in astrocytic processes regulates synaptic transmission and local blood flow essential for brain function. However, because of difficulties in imaging astrocytic processes, the subcellular spatial organization of mGluR-dependent Ca2+ signaling is not well characterized and its regulatory mechanism remains unclear. Using genetically encoded Ca2+ indicators, we showed that despite global stimulation by an mGluR agonist, astrocyte processes intrinsically exhibited a marked enrichment of Ca2+ responses. Immunocytochemistry indicated that these polarized Ca2+ responses could be attributed to increased density of surface mGluR5 on processes relative to the soma. Single-particle tracking of surface mGluR5 dynamics revealed a membrane barrier that blocked the movement of mGluR5 between the processes and the soma. Overexpression of mGluR or expression of its carboxyl terminus enabled diffusion of mGluR5 between the soma and the processes, disrupting the polarization of mGluR5 and of mGluR-dependent Ca2+ signaling. Together, our results demonstrate an mGluR5-selective diffusion barrier between processes and soma that compartmentalized mGluR Ca2+ signaling in astrocytes and may allow control of synaptic and vascular activity in specific subcellular domains.
<br/>来源：生物谷
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星形胶质细胞(astrocyte)之前被认为是神经元的辅助性细胞，如今研究人员发现它们自己能够给发送化学信号而不是电信号。它们将这些化学信号发送给神经元、血管细胞和其他星形胶质细胞来改善突触信号传送效率。日本理化研究所脑科学研究院研究员Katsuhiko Mikoshiba和Hiroko Bannai领导的一个研究小组描述了允许星形胶质细胞给它们网络中的每个细胞发送信号的机制。
<!--more-->
星形胶质细胞拥有一个位于中间的胞体(soma)和许多个射线状臂(ray-like arm)，而且这些射线状臂连接到它们调节的细胞上。健康的星形胶质细胞通过每个射线状臂发送相互独立的钙离子信号。已知这些信号受到细胞膜中一种被称作代谢型谷氨酸受体(metabotropic glutamate receptor, mGluR5)的受体的调节，但是科学家们不清楚的是如何将这些信号分解为单个钙离子信号。理解这种特异性可能在治疗上具有重要意义，这是因为在受到阿尔茨海默病或癫痫症影响的大脑中，星形胶质细胞发送全局性信号，打个比方而言，这种全局性信号更像是扩音器广播，而健康星形胶质细胞发送的信号类似于电话呼叫。
为了理解星形胶质细胞信号如何受到调节，研究人员对单个mGluR5受体进行量子点---当激发时能够发光的半导体纳米晶体---标记，然后观察这些受体如何穿过细胞膜。视频画面揭示mGluR5受体并不从射线状臂到达胞体。在正常星形胶质细胞中，mGluR5选择性扩散屏障能够通过钙离子信号区室化来允许每个射线状臂独立地调节它的接触伙伴。
为了研究这种扩散屏障的特征，Mikoshiba研究团队试图破坏它。过度表达的mGluR5覆盖着这种扩散屏障，据此，他们推断这种屏障是由与mGluR5胞质部分相互作用的蛋白组成的。每个屏障蛋白与单个mGluR5分子配对，从而阻止它跨到胞体中。然而，屏障蛋白的数量是有限的，过量的mGluR5让一些受体能够自由地跨进胞体，因而能够让全局性信号通过星形胶质细胞中的每个射线状臂。
阿尔茨海默病和癫痫症实验性动物模型证实星形胶质细胞拥有高浓度的mGlu5分子。研究人员相信理解这种扩散屏障的分子特征将有助于人们找到用于治疗这些疾病的新靶标。一旦揭示出这种屏障的分子特征，他们希望构建出一种缺乏星形胶质细胞屏障蛋白的转基因小鼠。Mikoshiba说，“我们非常吃惊地了解到全局性星形胶质细胞钙离子信号对神经元网络和神经-血管耦合(neuro-vascular coupling)的影响。”
本文编译自<a href="http://medicalxpress.com/news/2012-08-starring-role-astrocytes.html" target="_blank">A new starring role for astrocytes</a>
<div id="ztload">
<div> </div>
<div>
<div>
<img src="http://www.bioon.com/biology/UploadFiles/201208/2012081201392808.gif" alt="" width="113" height="149" border="0" />
<a title="" href="http://dx.doi.org/10.1126/scisignal.2002498" target="_blank">doi: 10.1126/scisignal.2002498</a>
PMC:
PMID:
</div>
<div>
<br/><strong>Receptor-Selective Diffusion Barrier Enhances Sensitivity of Astrocytic Processes to Metabotropic Glutamate Receptor Stimulation</strong><br/>
Misa Arizono1,2, Hiroko Bannai1*, Kyoko Nakamura3,4, Fumihiro Niwa1,5, Masahiro Enomoto1, Toru Matsu-ura1, Akitoshi Miyamoto1,2, Mark W. Sherwood1, Takeshi Nakamura3, and Katsuhiko Mikoshiba
Metabotropic glutamate receptor (mGluR)–dependent calcium ion (Ca2+) signaling in astrocytic processes regulates synaptic transmission and local blood flow essential for brain function. However, because of difficulties in imaging astrocytic processes, the subcellular spatial organization of mGluR-dependent Ca2+ signaling is not well characterized and its regulatory mechanism remains unclear. Using genetically encoded Ca2+ indicators, we showed that despite global stimulation by an mGluR agonist, astrocyte processes intrinsically exhibited a marked enrichment of Ca2+ responses. Immunocytochemistry indicated that these polarized Ca2+ responses could be attributed to increased density of surface mGluR5 on processes relative to the soma. Single-particle tracking of surface mGluR5 dynamics revealed a membrane barrier that blocked the movement of mGluR5 between the processes and the soma. Overexpression of mGluR or expression of its carboxyl terminus enabled diffusion of mGluR5 between the soma and the processes, disrupting the polarization of mGluR5 and of mGluR-dependent Ca2+ signaling. Together, our results demonstrate an mGluR5-selective diffusion barrier between processes and soma that compartmentalized mGluR Ca2+ signaling in astrocytes and may allow control of synaptic and vascular activity in specific subcellular domains.
<br/>来源：生物谷
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