The marginal cells of the Caenorhabditis elegans pharynx scavenge cholesterol and other hydrophobic small molecules

Abstract

The nematode 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 made by surrounding marginal cells. We find that many worm-bioactive small molecules ( a.k.a . wactives) accumulate inside of the marginal cells as crystals or globular spheres. Through screens for mutants that resist the lethality associated with one crystallizing wactive we identify a presumptive sphingomyelin-synthesis pathway that is necessary for crystal and sphere accumulation. We find that expression of sphingomyelin synthase 5 (SMS-5) in the marginal cells is not only sufficient for wactive accumulation but is also important for absorbing exogenous cholesterol, without which C. elegans cannot develop. We conclude that sphingomyelin-rich marginal cells act as a sink to scavenge important nutrients from filtered liquid that might otherwise be shunted back into the environment.

Cholesterol Regulates Innate Immunity via Nuclear Hormone Receptor NHR-8

“…These findings indicate that cholesterol is required for defense against infection and that cholesterol supplementation during animal development may not only boost the immune response but also improve the lifespan of the animals. (Chitwood and Lusby, 1991;Hieb and Rothstein, 1968) and requires different proteins to bind and transport cholesterol (Brown et al, 2008;Chen et al, 2016Chen et al, , 2019Huber et al, 2006;Kamal et al, 2019;Mé ndez-Acevedo et al, 2017;Ranawade et al, 2018;Sym et al, 2000;Valdes et al, 2012;Zhang et al, 2017). Thus, we investigated the roles of different transporters in the cholesterol-mediated immune response by exposing loss-of-function mutants in genes known to encode cholesterol transporters to P. aeruginosa.…”

Easy ultrastructural insight into the internal morphology of biological specimens by Atomic Force Microscopy

“…In case of the air-based dehydration of the immobilized ultra-sections of this study, the artifacts introduced by this technique seemed to be negligible when comparing the AFM results to available TEM data e.g. of C. elegans 11 – 17 as well as to results obtained in our lab employing an alternative and validated but far more complex dehydration technique (hexamethyldisilazane (HMDS) dehydration 36 , 43 , data not shown). The main reason for this might be given in the very small thickness of the prepared ultra-sections and their resulting tendency to dry rapidly.…”

“…By the combination of phase contrast light microscopy with AFM, the identification of specific tissues in C. elegans ultra-sections was easily carried out, resulting in timesaving and precise AFM image acquisition. Due to this, specific organs and tissues like the gonads 12 , the vulva 16 , the pharynx 17 or the intestine 11 were easily identified and afterwards imaged nanoscopically by AFM (Figs. 1 , 2 ).…”

Drug discovery: Insights from the invertebrate Caenorhabditis elegans

“…Drug ingestion is probably the main way through which xenobiotic molecules can gain access to target tissues in wild-type C. elegans. 132,133 However, the amphids, a pair of anterior sensory structures opened to the outside environment, and the vulva are also involved in drug and nanoparticles intake, respectively. 134,135 Moreover, the use of animals that have a compromised cuticle can significantly increase drug absorption.…”