MAPK-15 is a ciliary protein required for PKD-2 localization and male mating behavior in Caenorhabditis elegans.

Cilia are conserved cellular structures that facilitate sensory-based processes, including those required for neuronal and kidney functions. Here, we show that the human mitogen activated kinase-15 (MAPK-15) ortholog in Caenorhabditis elegans encodes a ciliary protein. A strain harboring a mutation in the catalytic site of the kinase domain results in ciliary-specific defects in tail neurons of both hermaphrodite and male worms, manifesting in dye uptake, dendrite extension, and male mating behavior defects. Transgenic-fusion constructs for two mapk-15 isoforms (A and C) with full-length kinase domains were generated. Expression of either the A- or C-specific isoform rescues the dye-filling and male-mating defective phenotypes, confirming the ciliary function of mapk-15. Expression of mapk-15 occurs in many ciliated-sensory neurons of the head and tail in hermaphrodite and male worms. Localization of MAPK-15 isoforms A and C occurs in the cell body, dendritic processes, and cilia. A C. elegans ortholog of polycystin-2, a protein that when defective in mammals results in autosomal dominant polycystic kidney disease, is mislocalized in the male ray neurons of mapk-15 mutant worms. Expression of the mapk-15 gene by the pkd-2 promoter partially rescues the male-mating defects observed in mapk-15 mutant animals. Expression of mapk-15 is DAF-19/RFX dependent in some CSNs and DAF-19/RFX independent in others. Collectively, these data suggest that MAPK-15 functions upstream of PKD-2 localization to modulate ciliary sensory functions.

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