The Marginal Cells of theCaenorhabditis elegansPharynx Scavenge Cholesterol and Other Hydrophobic Small Molecules

Abstract

One sentence summary: The anterior pharynx of C. elegans is a Sink for Hydrophobic Small Molecules AbstractThe nematode worm Caenorhabditis elegans is a bacterivore filter feeder. Through the contraction of the worm's pharynx, a bacterial suspension is sucked into the pharynx's lumen. Excess liquid is then shunted out of the buccal cavity through ancillary channels that are made from specialized pharyngeal cells called marginal cells. Through the characterization of our library of worm-bioactive small molecules (a.k.a. wactives), we found that more than one third of wactives visibly accumulate inside of the marginal cells as crystals or globular spheres. Wactives that visibly accumulate are typically more hydrophobic than those that do not. To understand why wactives accumulate specifically in marginal cells, we performed a forward genetic screen for mutants that resist the lethality associated with one crystallizing wactive. We identified a presumptive sphingomyelin-synthesis pathway that is necessary for crystal and sphere accumulation. Sphingomyelin is a phospholipid that is enriched in the outer leaflet of the plasma membranes of most metazoans. We find that the predicted terminal enzyme of this pathway, sphingomyelin synthase 5 (SMS-5), is expressed in the pharynx, contributes to sphingomyelin abundance, and that its expression in marginal cells is sufficient for wactive accumulation. We also find that the expression of SMS-5 in the marginal cells is necessary for the proper absorption of exogenous cholesterol, without which C. elegans cannot develop. We conclude that the sphingomyelin-rich plasma membrane of the marginal cells acts as a sink to scavenge important hydrophobic nutrients from the filtered liquid that might otherwise be shunted back into the environment.

Ciliary intrinsic mechanisms regulate dynamic ciliary extracellular vesicle release from sensory neurons

“…Ceramide is also an important lipid for cilia formation, ciliary length and ciliary signaling 19 . TTM-5 (Toxin-regulated Targets of MAPK 5) is an ortholog of human DEGS1/DEGS2 (delta 4-desaturase, sphingolipid) that plays a role in de novo ceramide synthesis [20][21][22] (Figures 4A). ttm-5 shows high expression in IL2 ciliated sensory neurons 23 , which are the sex-shared EV-releasing neurons (Figure S3B) and express ciliary EV biogenesis genes such as klp-6 and cil-7 [24][25][26] .…”