» Articles » PMID: 31477732

The Marginal Cells of the Caenorhabditis Elegans Pharynx Scavenge Cholesterol and Other Hydrophobic Small Molecules

Overview
Journal Nat Commun
Specialty Biology
Date 2019 Sep 4
PMID 31477732
Citations 9
Authors
Affiliations
Soon will be listed here.
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.

Citing Articles

A rapid in vivo pipeline to identify small molecule inhibitors of amyloid aggregation.

Kamal M, Knox J, Horne R, Tiwari O, Burns A, Han D Nat Commun. 2024; 15(1):8311.

PMID: 39333123 PMC: 11436953. DOI: 10.1038/s41467-024-52480-6.


Differential roles of lysosomal cholesterol transporters in the development of NMJs.

Guo A, Wu Q, Yan X, Chen K, Liu Y, Liang D Life Sci Alliance. 2024; 7(10).

PMID: 39084875 PMC: 11291935. DOI: 10.26508/lsa.202402584.


PGP-14 establishes a polar lipid permeability barrier within the C. elegans pharyngeal cuticle.

Kamal M, Tokmakjian L, Knox J, Han D, Moshiri H, Magomedova L PLoS Genet. 2023; 19(11):e1011008.

PMID: 37930961 PMC: 10653525. DOI: 10.1371/journal.pgen.1011008.


A spatiotemporal reconstruction of the pharyngeal cuticle reveals a structure rich in phase-separating proteins.

Kamal M, Tokmakjian L, Knox J, Mastrangelo P, Ji J, Cai H Elife. 2022; 11.

PMID: 36259463 PMC: 9629831. DOI: 10.7554/eLife.79396.


High-content approaches to anthelmintic drug screening.

Zamanian M, Chan J Trends Parasitol. 2021; 37(9):780-789.

PMID: 34092518 PMC: 8364491. DOI: 10.1016/j.pt.2021.05.004.


References
1.
Merris M, Kraeft J, Tint G, Lenard J . Long-term effects of sterol depletion in C. elegans: sterol content of synchronized wild-type and mutant populations. J Lipid Res. 2004; 45(11):2044-51. DOI: 10.1194/jlr.M400100-JLR200. View

2.
Yilmaz N, Yamaji-Hasegawa A, Hullin-Matsuda F, Kobayashi T . Molecular mechanisms of action of sphingomyelin-specific pore-forming toxin, lysenin. Semin Cell Dev Biol. 2017; 73:188-198. DOI: 10.1016/j.semcdb.2017.07.036. View

3.
Fang-Yen C, Avery L, Samuel A . Two size-selective mechanisms specifically trap bacteria-sized food particles in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2009; 106(47):20093-6. PMC: 2785297. DOI: 10.1073/pnas.0904036106. View

4.
Chachaty C, Rainteau D, Tessier C, Quinn P, Wolf C . Building up of the liquid-ordered phase formed by sphingomyelin and cholesterol. Biophys J. 2005; 88(6):4032-44. PMC: 1305634. DOI: 10.1529/biophysj.104.054155. View

5.
Hao L, Ben-David O, Babb S, Futerman A, Cohen B, Buttner E . Clozapine Modulates Glucosylceramide, Clears Aggregated Proteins, and Enhances ATG8/LC3 in Caenorhabditis elegans. Neuropsychopharmacology. 2016; 42(4):951-962. PMC: 5312067. DOI: 10.1038/npp.2016.230. View