Distribution and transport of cholesterol in Caenorhabditis elegans.
Cholesterol transport is an essential process in all multicellular organisms. In this study we applied two recently developed approaches to investigate the distribution and molecular mechanisms of cholesterol transport in Caenorhabditis elegans. The distribution of cholesterol in living worms was studied by imaging its fluorescent analog, dehydroergosterol, which we applied to the animals by feeding. Dehydroergosterol accumulates primarily in the pharynx, nerve ring, excretory gland cell, and gut of L1-L3 larvae. Later, the bulk of dehydroergosterol accumulates in oocytes and spermatozoa. Males display exceptionally strong labeling of spermatids, which suggests a possible role for cholesterol in sperm development. In a complementary approach, we used a photoactivatable cholesterol analog to identify cholesterol-binding proteins in C. elegans. Three major and several minor proteins were found specifically cross-linked to photocholesterol after UV irradiation. The major proteins were identified as vitellogenins. rme-2 mutants, which lack the vitellogenin receptor, fail to accumulate dehydroergosterol in oocytes and embryos and instead accumulate dehydroergosterol in the body cavity along with vitellogenin. Thus, uptake of cholesterol by C. elegans oocytes occurs via an endocytotic pathway involving yolk proteins. The pathway is a likely evolutionary ancestor of mammalian cholesterol transport.
Matyash
V
V
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
Geier
C
C
Henske
A
A
Mukherjee
S
S
Hirsh
D
D
Thiele
C
C
Grant
B
B
Maxfield
F R
FR
Kurzchalia
T V
TV
D000818:Animals; D005075:Biological Evolution; D001692:Biological Transport; D017173:Caenorhabditis elegans / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D004064:Digestive System / Q000378:metabolism; D004527:Egg Proteins; D004591:Electrophoresis, Polyacrylamide Gel; D004705:Endocytosis; D004875:Ergosterol / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics; D005260:Female; D008297:Male; D008856:Microscopy, Fluorescence; D008956:Models, Chemical; D009154:Mutation; D017830:Octoxynol; D010614:Pharynx / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology; D011233:Precipitin Tests; D011956:Receptors, Cell Surface / Q000378:metabolism; D013087:Spermatids / Q000378:metabolism; D013089:Spermatocidal Agents / Q000494:pharmacology; D013094:Spermatozoa / Q000378:metabolism*; D013261:Sterols / Q000378:metabolism; D013395:Sucrose / Q000378:metabolism; D014466:Ultraviolet Rays; D014819:Vitellogenins / Q000378:metabolism
D004527:Egg Proteins; D011956:Receptors, Cell Surface; D013089:Spermatocidal Agents; D013261:Sterols; D014819:Vitellogenins; C030474:vitellogenin receptor; C010905:dehydroergosterol; D011092:Polyethylene Glycols; D013395:Sucrose; D017830:Octoxynol; C010615:Nonidet P-40; D002784:Cholesterol; D004875:Ergosterol