新浪登录
腾讯登录Nature：磷脂酰肌醇在突触形成过程中的作用
| 导读 | <div id="region-column1and2-container-layout2">
<div>在中枢神经系统（central nervous system，CNS）的发育过程中，调控突触的数量和功能是至关重要的。本文研究组之前的研究表明，星形胶质细胞分泌的一些神经因子能促进兴奋性突触形成。其中凝血酶敏感素能够诱导形成突触结构，但是所形成的突... |
<div id="region-column1and2-container-layout2">
<div>在中枢神经系统（central nervous system，CNS）的发育过程中，调控突触的数量和功能是至关重要的。本文研究组之前的研究表明，星形胶质细胞分泌的一些神经因子能促进兴奋性突触形成。其中凝血酶敏感素能够诱导形成突触结构，但是所形成的突触不具备传导兴奋的功能。</div>
<div><!--more--></div>
<div id="region-column1and2-layout2">
在本文中，研究者证明，星形胶质细胞分泌的磷脂酰肌醇4（Gpc4）和磷脂酰肌醇6(Gpc6)能够诱导形成有功能的突触。在移除了Gpc4和Gpc6之后，星形胶质细胞分泌物诱导形成有功能的突触的能力受到了明显抑制。Gpc4能够增加突触活动的振幅和频率，这是通过增加突触后膜表面的GluA1亚型AMPA谷氨酸受体水平和受体富集来实现的，但并没有改变细胞内受体数量本身。在中枢神经系统发育的过程中，星形胶质细胞表达Gpc4和Gpc6，其中Gpc4富集在海马区，Gpc6富集在小脑。研究者证明，Gpc4不足会影响小鼠的突触的发育，具体表现为兴奋性电流振幅减弱和谷氨酸受体富集减少。
综上所述，在中枢神经系统的发育过程中，星形胶质细胞所分泌的磷脂酰肌醇家族成员是促进谷氨酸受体富集和诱导有功能突触形成的充要条件。
<img src="http://www.bioon.com/biology/UploadFiles/201205/20120530203244909.jpg" alt="" width="113" height="149" border="0" />
<div id="ztload">
<div>
<div>
<a title="" href="http://dx.doi.org/10.1038/nature11059" target="_blank">doi:10.1038/nature11059</a>
PMC:
PMID:
</div>
<div>
<br/><strong>Astrocyte glypicans 4 and 6 promote formation of excitatory synapses via GluA1 AMPA receptors</strong><br/>
Nicola J. Allen, Mariko L. Bennett, Lynette C. Foo, Gordon X. Wang, Chandrani Chakraborty, Stephen J. Smith & Ben A. Barres.
In the developing central nervous system (CNS), the control of synapse number and function is critical to the formation of neural circuits. We previously demonstrated that astrocyte-secreted factors powerfully induce the formation of functional excitatory synapses between CNS neurons1. Astrocyte-secreted thrombospondins induce the formation of structural synapses, but these synapses are postsynaptically silent2. Here we use biochemical fractionation of astrocyte-conditioned medium to identify glypican 4 (Gpc4) and glypican 6 (Gpc6) as astrocyte-secreted signals sufficient to induce functional synapses between purified retinal ganglion cell neurons, and show that depletion of these molecules from astrocyte-conditioned medium significantly reduces its ability to induce postsynaptic activity. Application of Gpc4 to purified neurons is sufficient to increase the frequency and amplitude of glutamatergic synaptic events. This is achieved by increasing the surface level and clustering, but not overall cellular protein level, of the GluA1 subunit of the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) glutamate receptor (AMPAR). Gpc4 and Gpc6 are expressed by astrocytes in vivo in the developing CNS, with Gpc4 expression enriched in the hippocampus and Gpc6 enriched in the cerebellum. Finally, we demonstrate that Gpc4-deficient mice have defective synapse formation, with decreased amplitude of excitatory synaptic currents in the developing hippocampus and reduced recruitment of AMPARs to synapses. These data identify glypicans as a family of novel astrocyte-derived molecules that are necessary and sufficient to promote glutamate receptor clustering and receptivity and to induce the formation of postsynaptically functioning CNS synapses.
</div>
</div>
</div>
<div><br/>来源：生物谷</div>
</div>
</div>
<div>在中枢神经系统（central nervous system，CNS）的发育过程中，调控突触的数量和功能是至关重要的。本文研究组之前的研究表明，星形胶质细胞分泌的一些神经因子能促进兴奋性突触形成。其中凝血酶敏感素能够诱导形成突触结构，但是所形成的突触不具备传导兴奋的功能。</div>
<div><!--more--></div>
<div id="region-column1and2-layout2">
在本文中，研究者证明，星形胶质细胞分泌的磷脂酰肌醇4（Gpc4）和磷脂酰肌醇6(Gpc6)能够诱导形成有功能的突触。在移除了Gpc4和Gpc6之后，星形胶质细胞分泌物诱导形成有功能的突触的能力受到了明显抑制。Gpc4能够增加突触活动的振幅和频率，这是通过增加突触后膜表面的GluA1亚型AMPA谷氨酸受体水平和受体富集来实现的，但并没有改变细胞内受体数量本身。在中枢神经系统发育的过程中，星形胶质细胞表达Gpc4和Gpc6，其中Gpc4富集在海马区，Gpc6富集在小脑。研究者证明，Gpc4不足会影响小鼠的突触的发育，具体表现为兴奋性电流振幅减弱和谷氨酸受体富集减少。
综上所述，在中枢神经系统的发育过程中，星形胶质细胞所分泌的磷脂酰肌醇家族成员是促进谷氨酸受体富集和诱导有功能突触形成的充要条件。
<img src="http://www.bioon.com/biology/UploadFiles/201205/20120530203244909.jpg" alt="" width="113" height="149" border="0" />
<div id="ztload">
<div>
<div>
<a title="" href="http://dx.doi.org/10.1038/nature11059" target="_blank">doi:10.1038/nature11059</a>
PMC:
PMID:
</div>
<div>
<br/><strong>Astrocyte glypicans 4 and 6 promote formation of excitatory synapses via GluA1 AMPA receptors</strong><br/>
Nicola J. Allen, Mariko L. Bennett, Lynette C. Foo, Gordon X. Wang, Chandrani Chakraborty, Stephen J. Smith & Ben A. Barres.
In the developing central nervous system (CNS), the control of synapse number and function is critical to the formation of neural circuits. We previously demonstrated that astrocyte-secreted factors powerfully induce the formation of functional excitatory synapses between CNS neurons1. Astrocyte-secreted thrombospondins induce the formation of structural synapses, but these synapses are postsynaptically silent2. Here we use biochemical fractionation of astrocyte-conditioned medium to identify glypican 4 (Gpc4) and glypican 6 (Gpc6) as astrocyte-secreted signals sufficient to induce functional synapses between purified retinal ganglion cell neurons, and show that depletion of these molecules from astrocyte-conditioned medium significantly reduces its ability to induce postsynaptic activity. Application of Gpc4 to purified neurons is sufficient to increase the frequency and amplitude of glutamatergic synaptic events. This is achieved by increasing the surface level and clustering, but not overall cellular protein level, of the GluA1 subunit of the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) glutamate receptor (AMPAR). Gpc4 and Gpc6 are expressed by astrocytes in vivo in the developing CNS, with Gpc4 expression enriched in the hippocampus and Gpc6 enriched in the cerebellum. Finally, we demonstrate that Gpc4-deficient mice have defective synapse formation, with decreased amplitude of excitatory synaptic currents in the developing hippocampus and reduced recruitment of AMPARs to synapses. These data identify glypicans as a family of novel astrocyte-derived molecules that are necessary and sufficient to promote glutamate receptor clustering and receptivity and to induce the formation of postsynaptically functioning CNS synapses.
</div>
</div>
</div>
<div><br/>来源：生物谷</div>
</div>
</div>
还没有人评论，赶快抢个沙发