General and cell-type specific mechanisms target TRPP2/PKD-2 to cilia
General and cell-type specific mechanisms target TRPP2/PKD-2 to cilia
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DOI：
10.1242/dev.02555
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发表时间：
2006-10-01
期刊：
影响因子：
4.6
通讯作者：
Barr, Maureen M.
中科院分区：
文献类型：
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作者：
Bae, Young-Kyung;Qin, Hongmin;Barr, Maureen M.
瞬时受体电位多囊蛋白2通道（TRPP 2/PKD-2）的纤毛定位在进化上是保守的，但TRPP 2如何靶向纤毛尚不清楚。在这项研究中，我们的特点PKD-2，TRPP 2同源物，在C。感觉神经元我们证明了GFP标记的PKD-2在树突状隔室中双向移动。此外，我们显示了不同的分子在调节PKD-2的纤毛定位的要求。PKD-2通过AP-I/AP-1复合物引导树突状颗粒移动。当在非天然神经元中表达时，PKD-2保留在细胞体中，并且在树突或纤毛中未观察到，这表明将PKD-2引导至树突需要细胞类型特异性因子。PKD-2在纤毛和细胞体中的稳定需要LOV-1，一种功能伴侣和TRPP 1同源物。在lov-1突变体中，PKD-2在纤毛中大大减少，并在神经元细胞体中形成异常聚集体。鞭毛内转运（IFT）不是必不可少的PKD-2树突运动或进入纤毛，但可能调节PKD-2纤毛丰度。我们建议，一般和细胞类型特异性因素支配TRPP 2/PKD-2亚细胞分布，形成至少两个步骤，涉及体树突和纤毛排序的决定。
Ciliary localization of the transient receptor potential polycystin 2 channel (TRPP2/PKD-2) is evolutionarily conserved, but how TRPP2 is targeted to cilia is not known. In this study, we characterize the motility and localization of PKD-2, a TRPP2 homolog, in C. elegans sensory neurons. We demonstrate that GFP-tagged PKD-2 moves bidirectionally in the dendritic compartment. Furthermore, we show a requirement for different molecules in regulating the ciliary localization of PKD-2. PKD-2 is directed to moving dendritic particles by the UNC-101/adaptor protein 1 (AP-1) complex. When expressed in non-native neurons, PKD-2 remains in cell bodies and is not observed in dendrites or cilia, indicating that cell-type specific factors are required for directing PKD-2 to the dendrite. PKD-2 stabilization in cilia and cell bodies requires LOV-1, a functional partner and a TRPP1 homolog. In lov-1 mutants, PKD-2 is greatly reduced in cilia and forms abnormal aggregates in neuronal cell bodies. Intraflagellar transport ( IFT) is not essential for PKD-2 dendritic motility or access to the cilium, but may regulate PKD-2 ciliary abundance. We propose that both general and cell-type-specific factors govern TRPP2/PKD-2 subcellular distribution by forming at least two steps involving somatodendritic and ciliary sorting decisions.