Astrocyte-derived small extracellular vesicles promote synapse formation via fibulin-2-mediated TGF-β signaling.
Astrocyte-derived small extracellular vesicles promote synapse formation via fibulin-2-mediated TGF-β signaling.
复制标题
DOI：
10.1016/j.celrep.2021.108829
复制
发表时间：
2021-03-09
期刊：
影响因子：
8.8
通讯作者：
Weaver AM
中科院分区：
文献类型：
--
作者：
Patel MR;Weaver AM
神经元突触的形成对大脑发育至关重要，并依赖于星形胶质细胞分泌的因子。在这里，我们报告说，小细胞外囊泡（EV）分泌的初级星形胶质细胞，但不是从神经元或C6胶质瘤细胞，大大提高脊柱和突触形成的初级皮层神经元。对来自星形胶质细胞、神经元和C6胶质瘤细胞的小EV的比较蛋白质组学分析将fibulin-2鉴定为调节突触发生的有希望的EV货物。用重组fibulin-2处理皮质神经元增加了棘和突触的形成，类似于小EV的效果。此外，用fibulin-2或星形胶质细胞衍生的小EV处理神经元导致Smad 2磷酸化增加，Smad 2是TGF-β信号传导的指标。最后，通过抑制转化生长因子β（TGF-β）信号转导，fibulin-2和星形胶质细胞来源的小EV对突触形成的影响被逆转。这些数据表明了一种模型，其中星形胶质细胞EV通过纤蛋白-2介导的TGF-β信号传导的活化促进突触形成。Patel和Weaver为星形胶质细胞衍生的小细胞外囊泡（SEV）在初级皮质神经元突触发生中的功能提供了证据。星形胶质细胞衍生的SEV在SEV的表面上携带纤蛋白-2，其导致神经元中TGF-β信号传导的激活。纤蛋白-2驱动的TGF-β信号传导驱动树突棘和突触形成。
Neuronal synapse formation is critical for brain development and depends on secreted factors from astrocytes. Here, we report that small extracellular vesicles (EVs) secreted from primary astrocytes, but not from neurons or C6 glioma cells, greatly enhance spine and synapse formation by primary cortical neurons. A comparative proteomics analysis of small EVs from astrocytes, neurons, and C6 glioma cells identified fibulin-2 as a promising EV cargo to regulate synaptogenesis. Treatment of cortical neurons with recombinant fibulin-2 increased the formation of spines and synapses, similar to the effect of small EVs. In addition, treatment of neurons with fibulin-2 or astrocyte-derived small EVs led to increased phosphorylation of Smad2, an indicator of TGF-β signaling. Finally, the effects of fibulin-2 and astrocyte-derived small EVs on synapse formation were reversed by inhibiting transforming growth factor β (TGF-β) signaling. These data suggest a model in which astrocyte EVs promote synapse formation via fibulin-2-mediated activation of TGF-β signaling. Patel and Weaver provide evidence for the function of astrocyte-derived small extracellular vesicles (SEVs) in synaptogenesis of primary cortical neurons. Astrocyte-derived SEVs carry fibulin-2 on the surface of SEVs that leads to activation of TGF-β signaling in neurons. The fibulin-2-driven TGF-β signaling drives dendritic spine and synapse formation.
登录
查看更多内容
影响因子：
16
作者：
Lötvall J;Hill AF;Hochberg F;Buzás EI;Di Vizio D;Gardiner C;Gho YS;Kurochkin IV;Mathivanan S;Quesenberry P;Sahoo S;Tahara H;Wauben MH;Witwer KW;Théry C
通讯作者：
Théry C
影响因子：
3.9
作者：
Costanza B;Umelo IA;Bellier J;Castronovo V;Turtoi A
通讯作者：
Turtoi A
影响因子：
4.4
作者：
Jimenez, Lizandra;Yu, Hui;Weaver, Alissa M.
通讯作者：
Weaver, Alissa M.
DOI：
10.1007/978-1-61779-452-0_22
发表时间：
2012-01-01
期刊：
ASTROCYTES: METHODS AND PROTOCOLS
影响因子：
--
作者：
Jones, Emma V.;Cook, Denise;Murai, Keith K.
通讯作者：
Murai, Keith K.
影响因子：
16.6
作者：
Lai, Charles P.;Kim, Edward Y.;Badr, Christian E.;Weissleder, Ralph;Mempel, Thorsten R.;Tannous, Bakhos A.;Breakefield, Xandra O.
通讯作者：
Breakefield, Xandra O.