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Vol. 12, Issue 6, 1725-1736, June 2001

Distribution and Transport of Cholesterol in Caenorhabditis elegans

Vitali Matyash,^* Christian Geier, Annemarie Henske,^* Sushmita Mukherjee,^§ David Hirsh, Christoph Thiele,^* Barth Grant, Frederick R. Maxfield,^§ and Teymuras V. Kurzchalia^*¶

 ^*Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany;  Max-Delbrück Centre for Molecular Medicine and Franz-Volhard-Clinic, Berlin-Buch, Germany;  ^§Department of Biochemistry, Cornell University Medical College, New York, New York 100214; and  Department of Biochemistry and Molecular Biophysics, Columbia University College of Physicians and Surgeons, New York, New York 10032

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.

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^¶ Corresponding author. E-mail address: kurzchalia{at}mpi-cbg.de.

These authors contributed equally to this work.

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Molecular Biology of the Cell
Vol. 12, 1725-1736, June 2001
Copyright © 2001 by The American Society for Cell Biology

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