The retinitis pigmentosa protein RP2 links pericentriolar vesicle transport between the Golgi and the primary cilium
The retinitis pigmentosa protein RP2 links pericentriolar vesicle transport between the Golgi and the primary cilium
复制标题
DOI：
10.1093/hmg/ddq012
复制
发表时间：
2010-04-01
影响因子：
3.5
通讯作者：
Cheetham, Michael E.
中科院分区：
文献类型：
--
作者：
Evans, R. Jane;Schwarz, Nele;Cheetham, Michael E.
光感受器是复杂的纤毛感觉神经元。光感受器的基体和睫状体周围脊与高尔基复合体一起发挥作用，调节蛋白质从内节到外节感觉轴丝的输出。在这里，我们发现视网膜色素变性蛋白 RP2 是 Arl3 的 GTP 酶激活蛋白 (GAP)，定位于睫状体，即基体和感光器纤毛基部的相关中心粒。靶向睫状体基部依赖于 N 末端肉豆蔻酰化。 RP2 还定位于高尔基体和光感受器的纤毛周围脊，这表明 RP2 在调节囊泡运输和对接中发挥作用。为了探索这一假设，我们研究了 RP2 耗竭和 Arl3 (Q71L) 组成型活性形式的表达对中心粒周围囊泡运输的影响。 Kif3a 是鞭毛内运输 (IFT) 的一个组成部分，对于纤毛维持和通过光感受器中连接纤毛的蛋白质运输非常重要。与 Kif3a 和 Arl3 耗竭类似，RP2 的缺失会导致高尔基体网络破碎。 RP2 的消耗和 Arl3 的失调导致囊泡循环货物从高尔基复合体分散到纤毛，包括 IFT 蛋白 IFT20。我们认为，RP2 对 Arl3 的调节对于维持高尔基体凝聚力、促进囊泡的运输和对接非常重要，从而将蛋白质携带到连接纤毛的光感受器基部，以便运输到外段。
Photoreceptors are complex ciliated sensory neurons. The basal body and periciliary ridge of photoreceptors function in association with the Golgi complex to regulate the export of proteins from the inner segment to the outer segment sensory axoneme. Here, we show that the retinitis pigmentosa protein RP2, which is a GTPase activating protein (GAP) for Arl3, localizes to the ciliary apparatus, namely the basal body and the associated centriole at the base of the photoreceptor cilium. Targeting to the ciliary base was dependent on N-terminal myristoylation. RP2 also localized to the Golgi and periciliary ridge of photoreceptors, which suggested a role for RP2 in regulating vesicle traffic and docking. To explore this hypothesis, we investigated the effect of RP2 depletion and the expression of a constitutively active form of Arl3 (Q71L) on pericentriolar vesicle transport. Kif3a, a component of intraflagellar transport (IFT), is important in cilia maintenance and transport of proteins through the connecting cilium in photoreceptors. Similar to Kif3a and Arl3 depletion, loss of RP2 led to fragmentation of the Golgi network. Depletion of RP2 and dysregulation of Arl3 resulted in dispersal of vesicles cycling cargo from the Golgi complex to the cilium, including the IFT protein IFT20. We propose that RP2 regulation of Arl3 is important for maintaining Golgi cohesion, facilitating the transport and docking of vesicles and thereby carrying proteins to the base of the photoreceptor connecting cilium for transport to the outer segment.