General and cell-type specific mechanisms target TRPP2/PKD-2 to cilia

被引:81
作者
Bae, Young-Kyung
Qin, Hongmin
Knobel, Karla M.
hu, Jinga Hu
Rosenbaum, Joel L.
Barr, Maureen M. [1 ]
机构
[1] Univ Wisconsin, Div Pharmaceut Sci, Genet Lab, Madison, WI 53705 USA
[2] Univ Wisconsin, Div Pharmaceut Sci, Sch Pharm, Madison, WI 53705 USA
[3] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06511 USA
来源
DEVELOPMENT | 2006年 / 133卷 / 19期
关键词
autosomal dominant polycystic kidney disease; C; elegans; TRPP2 ( PKD2)/PKD-2;
D O I
10.1242/dev.02555
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:3859 / 3870
页数:12
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