Spatial targeting of type II protein kinase A to filopodia mediates the regulation of growth cone guidance by cAMP
Spatial targeting of type II protein kinase A to filopodia mediates the regulation of growth cone guidance by cAMP
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DOI：
10.1083/jcb.200607128
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发表时间：
2007-01-01
影响因子：
7.8
通讯作者：
Zheng, James Q.
中科院分区：
文献类型：
--
作者：
Han, Jianzhong;Han, Liang;Zheng, James Q.
第二信使环磷酸腺苷（cAMP）在轴突生长和指导中起着关键作用，但其下游机制仍然不清楚。在这项研究中，我们报告了11型蛋白激酶A（PKA）在生长锥丝状伪足中高度富集，这种空间定位使得cAMP信号能够与其特定效应器偶联，以调节引导反应。破坏PKA定位到丝状伪足损害cAMP介导的生长锥吸引力，并防止通过升高的cAMP将排斥反应转换为吸引力。我们的数据进一步表明，PKA靶向蛋白磷酸酶-1（PP 1）通过磷酸化的调节蛋白抑制剂-1（1 -1），以促进生长锥吸引。最后，我们发现l-1和PP 1介导髓鞘相关糖蛋白诱导的生长锥排斥。这些结果表明，生长锥丝状伪足的II型PKA的空间定位在生长锥运动的调节和cAMP的引导中起着重要作用。
The second messenger cyclic adenosine monophosphate (cAMP) plays a pivotal role in axonal growth and guidance, but its downstream mechanisms remain elusive. In this study, we report that type 11 protein kinase A (PKA) Is highly enriched in growth cone filopodia, and this spatial localization enables the coupling of cAMP signaling to its specific effectors to regulate guidance responses. Disrupting the localization of PKA to filopodia impairs cAMP-mediated growth cone attraction and prevents the switching of repulsive responses to attraction by elevated cAMP. Our data further show that PKA targets protein phosphatase-1 (PP1) through the phosphorylation of a regulatory protein inhibitor-1 (l-1) to promote growth cone attraction. Finally, we find that l-1 and PP1 mediate growth cone repulsion induced by myelin-associated glycoprotein. These findings demonstrate that the spatial localization of type II PKA to growth cone filopodia plays an important role In the regulation of growth cone motility and guidance by cAMP.