PTPμ signaling via PKCδ is instructive for retinal ganglion cell guidance
PTPμ signaling via PKCδ is instructive for retinal ganglion cell guidance
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DOI：
10.1016/j.mcn.2003.12.003
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发表时间：
2004-04-01
影响因子：
3.5
通讯作者：
Brady-Kalnay, SM
中科院分区：
文献类型：
--
作者：
Ensslen, SE;Brady-Kalnay, SM
受体蛋白酪氨酸磷酸酶（RPTP）PTPmu介导鼻侧和颞侧视网膜神经节细胞（RGC）轴突中不同的细胞反应。PTPmu允许鼻RGC神经突生长并抑制颞RGC。此外，PTPmu导致优先的时间生长锥崩溃。先前的研究表明，PTPmu与鸡视网膜中的支架蛋白RACK 1和蛋白激酶C-δ（PKC δ）亚型相关，并且PKC δ活性是PTPmu介导的RGC生长所必需的。使用在体外条纹和崩溃分析，我们发现，PKC δ活性是所需的抑制和允许的反应RGCs PTPmu，与较高水平的PKC δ激活与时间生长锥崩溃和排斥。差异PKC δ激活的潜在机制是由于视网膜中PTPmu表达的梯度。PTPmu在视网膜中以高颞、低鼻阶梯度表达。为了支持这一点，鼻神经突中外源性PTPmu的过表达导致响应于PTPmu的表型从允许转换为排斥。总之，这些结果表明，PTPmu在视网膜内的差异表达对于RGC指导是有指导意义的，并且响应于PTPmu信号传导的PKC δ激活的幅度导致鼻和颞RGC的不同细胞行为。(C)2004年爱思唯尔公司All rights reserved.
The receptor protein tyrosine phosphatase (RPTP) PTPmu mediates distinct cellular responses in nasal and temporal retinal ganglion cell (RGC) axons. PTPmu is permissive for nasal RGC neurite outgrowth and inhibitory to temporal RGCs. In addition, PTPmu causes preferential temporal growth cone collapse. Previous studies demonstrated that PTPmu associates with the scaffolding protein RACK1 and the protein kinase C-delta (PKCdelta) isoform in chick retina and that PKCdelta activity is required for PTPmu-mediated RGC outgrowth. Using in vitro stripe and collapse assays, we find that PKCdelta activity is required for both inhibitory and permissive responses of RGCs to PTPmu, with higher levels of PKCdelta activation associated with temporal growth cone collapse and repulsion. A potential mechanism for differential PKCdelta activation is due to the gradient of PTPmu expression in the retina. PTPmu is expressed in a high temporal, low nasal step gradient in the retina. In support of this, overexpression of exogenous PTPmu in nasal neurites results in a phenotypic switch from permissive to repulsive in response to PTPmu. Together, these results suggest that the differential expression of PTPmu within the retina is instructive for RGC guidance and that the magnitude of PKCdelta activation in response to PTPmu signaling results in the distinct cellular behaviors of nasal and temporal RGCs. (C) 2004 Elsevier Inc. All rights reserved.