Bidirectional interactions between NOX2-type NADPH oxidase and the F-actin cytoskeleton in neuronal growth cones.
Bidirectional interactions between NOX2-type NADPH oxidase and the F-actin cytoskeleton in neuronal growth cones.
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DOI：
10.1111/jnc.12734
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发表时间：
2014-08
影响因子：
4.7
通讯作者：
Suter DM
中科院分区：
文献类型：
--
作者：
Munnamalai V;Weaver CJ;Weisheit CE;Venkatraman P;Agim ZS;Quinn MT;Suter DM
NADPH氧化酶对神经元功能很重要，但详细的亚细胞定位研究尚未进行。在这里，我们首次提供了神经元生长锥中存在功能性nox2型NADPH氧化酶复合物及其与肌动蛋白细胞骨架的双向关系的证据。NADPH氧化酶抑制导致f -肌动蛋白含量降低，f -肌动蛋白逆行流动和神经突生长。通过激活蛋白激酶C刺激NADPH氧化酶增加了生长锥周围过氧化氢的水平。NADPH氧化酶的主要亚基NOX2/gp91phox定位于生长锥质膜上，与调控亚基p40phox重叠较少。P40phox本身与丝状肌动蛋白束共定位。差异亚细胞分离显示NOX2/gp91phox和p40phox分别与膜和细胞骨架部分优先关联。当用包被细胞粘附分子apCAM的小珠诱导神经突生长时，我们观察到p40phox与NOX2/gp91phox在apCAM粘附位点的共定位显著增加。总之，这些发现表明NADPH氧化酶活性与神经元生长锥中肌动蛋白细胞骨架之间存在双向功能关系，这有助于控制神经突的生长。
NADPH oxidases are important for neuronal function but detailed subcellular localization studies have not been performed. Here, we provide the first evidence for the presence of functional NOX2-type NADPH oxidase complex in neuronal growth cones and its bidirectional relationship with the actin cytoskeleton. NADPH oxidase inhibition resulted in reduced F-actin content, retrograde F-actin flow, and neurite outgrowth. Stimulation of NADPH oxidase via protein kinase C activation increased levels of hydrogen peroxide in the growth cone periphery. The main enzymatic NADPH oxidase subunit NOX2/gp91phox localized to the growth cone plasma membrane and showed little overlap with the regulatory subunit p40phox. p40phox itself exhibited co-localization with filopodial actin bundles. Differential subcellular fractionation revealed preferential association of NOX2/gp91phox and p40phox with the membrane and the cytoskeletal fraction, respectively. When neurite growth was evoked with beads coated with the cell adhesion molecule apCAM, we observed a significant increase in co-localization of p40phox with NOX2/gp91phox at apCAM adhesion sites. Together, these findings suggest a bidirectional functional relationship between NADPH oxidase activity and the actin cytoskeleton in neuronal growth cones, which contributes to the control of neurite outgrowth.
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影响因子：
2.7
作者：
Cao, Xian;Demel, Stacie L.;Quinn, Mark T.;Galligan, James J.;Kreulen, David
通讯作者：
Kreulen, David
影响因子：
8
作者：
Altenhofer, Sebastian;Kleikers, Pamela W. M.;Radermacher, Kim A.;Scheurer, Peter;Hermans, J. J. Rob;Schiffers, Paul;Ho, Heidi;Wingler, Kirstin;Schmidt, Harald H. H. W.
通讯作者：
Schmidt, Harald H. H. W.
影响因子：
3.3
作者：
Kim, Jun-Sub;Huang, Timothy Y.;Bokoch, Gary M.
通讯作者：
Bokoch, Gary M.
影响因子：
3.4
作者：
Kawahara, Tsukasa;Quinn, Mark T.;Lambeth, J. David
通讯作者：
Lambeth, J. David
DOI：
10.1083/jcb.201102095
发表时间：
2011-07-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Finkel T
通讯作者：
Finkel T