Astroglial exosome HepaCAM signaling and ApoE antagonization coordinates early postnatal cortical pyramidal neuronal axon growth and dendritic spine formation.
Astroglial exosome HepaCAM signaling and ApoE antagonization coordinates early postnatal cortical pyramidal neuronal axon growth and dendritic spine formation.
复制标题
星形胶质细胞外泌体 HepaCAM 信号传导和 ApoE 拮抗作用协调出生后早期皮质锥体神经元轴突生长和树突棘形成。
DOI：
10.1101/2023.02.14.528554
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Yang,Yongjie
中科院分区：
文献类型：
--
作者：
Jin,Shijie;Chen,Xuan;Tian,Yang;Jarvis,Rachel;Promes,Vanessa;Yang,Yongjie
发育中的星形胶质细胞通过分泌和接触信号在调节突触发生中发挥重要作用。它们是否调节产后轴突生长尚不清楚。通过使用尺寸排阻色谱（SEC）选择性分离外泌体并使用细胞类型特异性外泌体报告小鼠，我们目前的结果定义了一种分泌的星形胶质细胞外泌体途径，该途径可以在体内长距离传播并刺激皮质锥体神经元的轴突生长。随后的生化和遗传学研究发现，神经胶质HepaCAM蛋白的表面表达本质上充分介导了星形胶质细胞外泌体的轴突刺激作用。有趣的是，载脂蛋白E（ApoE）是星形胶质细胞分泌的促进突触发生的主要胆固醇载体，它强烈抑制星形胶质细胞外泌体对轴突生长的刺激作用。发育性 ApoE 缺陷也会显着降低皮质锥体神经元的棘密度。总之，我们的研究表明星形胶质细胞外泌体在调节轴突生长及其 ApoE 拮抗作用中存在表面接触机制，ApoE 共同协调出生后早期锥体神经元轴突生长和树突棘形成。
Developing astroglia play important roles in regulating synaptogenesis through secreted and contact signals. Whether they regulate postnatal axon growth is unknown. By selectively isolating exosomes using size-exclusion chromatography (SEC) and employing cell-type specific exosome reporter mice, our current results define a secreted astroglial exosome pathway that can spread long-range in vivo and stimulate axon growth of cortical pyramidal neurons. Subsequent biochemical and genetic studies found that surface expression of glial HepaCAM protein essentially and sufficiently mediates the axon-stimulating effect of astroglial exosomes. Interestingly, apolipoprotein E (ApoE), a major astroglia-secreted cholesterol carrier to promote synaptogenesis, strongly inhibits the stimulatory effect of astroglial exosomes on axon growth. Developmental ApoE deficiency also significantly reduces spine density of cortical pyramidal neurons. Together, our study suggests a surface contact mechanism of astroglial exosomes in regulating axon growth and its antagonization by ApoE, which collectively coordinates early postnatal pyramidal neuronal axon growth and dendritic spine formation.