ABSTRACT
Cell size and biosynthetic capacity generally increase with increased DNA content. Polyploidy has therefore been proposed to be an adaptive strategy to increase cell size in specialized tissues with high biosynthetic demands. However, if and how DNA concentration limits cellular biosynthesis in vivo is not well understood, and the impacts of polyploidy in non-disease states is not well studied. Here, we show that polyploidy in the C. elegans intestine is critical for cell growth and yolk biosynthesis, a central role of this organ. Artificially lowering the DNA/cytoplasm ratio by reducing polyploidization in the intestine gave rise to smaller cells with more dilute mRNA. Highly-expressed transcripts were more sensitive to this mRNA dilution, whereas lowly-expressed genes were partially compensated - in part by loading more RNA Polymerase II on the remaining genomes. DNA-dilute cells had normal total protein concentration, which we propose is achieved by increasing production of translational machinery at the expense of specialized, cell-type specific proteins.
ABSTRACT
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.
