General and cell-type specific mechanisms target TRPP2/PKD-2 to cilia.
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.
Bae
Young-Kyung
YK
Laboratory of Genetics, Division of Pharmaceutical Sciences, University of Wisconsin-Madison, Madison, WI 53705-2222, USA.
Qin
Hongmin
H
Knobel
Karla M
KM
Hu
Jinghua
J
Rosenbaum
Joel L
JL
Barr
Maureen M
MM
D033961:Adaptor Protein Complex 1 / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism* / Q000648:ultrastructure; D029742:Caenorhabditis elegans Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002923:Cilia / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D003712:Dendrites / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism; D005260:Female; D005407:Flagella / Q000737:chemistry / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000032:analysis; D008297:Male; D009475:Neurons, Afferent / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D021381:Protein Transport; D050396:TRPP Cation Channels / Q000032:analysis / Q000378:metabolism*
D033961:Adaptor Protein Complex 1; D029742:Caenorhabditis elegans Proteins; D049452:Green Fluorescent Proteins; D050396:TRPP Cation Channels; C515011:LOV-1 protein, C elegans; C085440:UNC-101 protein, C elegans