Astrocytic αVβ3 integrin inhibits neurite outgrowth and promotes retraction of neuronal processes by clustering Thy-1.
Astrocytic αVβ3 integrin inhibits neurite outgrowth and promotes retraction of neuronal processes by clustering Thy-1.
复制标题
DOI：
10.1371/journal.pone.0034295
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Leyton L
中科院分区：
文献类型：
--
作者：
Herrera-Molina R;Frischknecht R;Maldonado H;Seidenbecher CI;Gundelfinger ED;Hetz C;Aylwin Mde L;Schneider P;Quest AF;Leyton L
Thy-1是一种膜糖蛋白，被认为可以稳定或抑制神经元突起的生长。然而，其确切的功能仍然不清楚，因为其内源性配体是未知的。我们以前发现Thy-1在星形胶质细胞的反式诱导反应中直接与αVβ3整联蛋白结合。尽管如此，αVβ3整联蛋白是否也可能作为Thy-1-配体触发神经元反应尚未探讨。因此，利用原代神经元和神经元衍生的细胞系CAD，测试了Thy-1介导的αVβ3整联蛋白对神经元突起生长和收缩的作用。在星形胶质细胞-神经元共培养中，内源性αVβ3整合素限制神经突生长。同样，αVβ3-Fc足以抑制Thy-1（+）中的神经突延伸，但不能抑制Thy-1（-）CAD细胞中的神经突延伸。在分化暴露于αVβ3-Fc的原代神经元中，检测到更少和更短的树突。这种效果被废除的切割Thy-1从神经元表面使用磷酸肌醇特异性磷脂酶C（PI-PLC）。此外，αVβ3-Fc还诱导分化的CAD细胞中已经延伸的Thy-1（+）-轴突样神经突以及分化的原代神经元中的轴突终末的回缩。当αVβ3整合素诱导Thy-1分子在质膜上重新分布和聚集时，轴突发生收缩。在原代神经元轴突回缩过程中，在Thy-1簇中检测到αVβ3-Fc的结合。此外，αVβ3-Fc诱导的Thy-1聚集与Src激酶的再分布和失活在时间和空间上相关。因此，我们的数据表明，αVβ3整联蛋白是Thy-1的配体，结合后不仅限制神经突的生长，而且通过诱导Thy-1簇集诱导已经存在的过程的收缩。我们认为，这些事件参与双向星形胶质细胞神经元通信相关的轴突修复后神经元损伤。
Thy-1 is a membrane glycoprotein suggested to stabilize or inhibit growth of neuronal processes. However, its precise function has remained obscure, because its endogenous ligand is unknown. We previously showed that Thy-1 binds directly to αVβ3 integrin in trans eliciting responses in astrocytes. Nonetheless, whether αVβ3 integrin might also serve as a Thy-1-ligand triggering a neuronal response has not been explored. Thus, utilizing primary neurons and a neuron-derived cell line CAD, Thy-1-mediated effects of αVβ3 integrin on growth and retraction of neuronal processes were tested. In astrocyte-neuron co-cultures, endogenous αVβ3 integrin restricted neurite outgrowth. Likewise, αVβ3-Fc was sufficient to suppress neurite extension in Thy-1(+), but not in Thy-1(−) CAD cells. In differentiating primary neurons exposed to αVβ3-Fc, fewer and shorter dendrites were detected. This effect was abolished by cleavage of Thy-1 from the neuronal surface using phosphoinositide-specific phospholipase C (PI-PLC). Moreover, αVβ3-Fc also induced retraction of already extended Thy-1(+)-axon-like neurites in differentiated CAD cells as well as of axonal terminals in differentiated primary neurons. Axonal retraction occurred when redistribution and clustering of Thy-1 molecules in the plasma membrane was induced by αVβ3 integrin. Binding of αVβ3-Fc was detected in Thy-1 clusters during axon retraction of primary neurons. Moreover, αVβ3-Fc-induced Thy-1 clustering correlated in time and space with redistribution and inactivation of Src kinase. Thus, our data indicates that αVβ3 integrin is a ligand for Thy-1 that upon binding not only restricts the growth of neurites, but also induces retraction of already existing processes by inducing Thy-1 clustering. We propose that these events participate in bi-directional astrocyte-neuron communication relevant to axonal repair after neuronal damage.
登录
查看更多内容
DOI：
10.1016/j.bbamcr.2008.10.004
发表时间：
2009-05
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Barker TH;Hagood JS
通讯作者：
Hagood JS
影响因子：
3.3
作者：
Baudouin, Stephane J.;Angibaud, Julie;Boudin, Helene
通讯作者：
Boudin, Helene
影响因子：
4
作者：
Henriquez, Mauricio;Herrera-Molina, Rodrigo;Leyton, Lisette
通讯作者：
Leyton, Lisette
影响因子：
21.3
作者：
Brouns, MR;Matheson, SF;Settleman, J
通讯作者：
Settleman, J
影响因子：
7.8
作者：
Chen, Yun;Thelin, William R.;Jacobson, Ken
通讯作者：
Jacobson, Ken