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First published online May 10, 2006
doi: 10.1242/10.1242/jcs.02911

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Cholesterol contributes to the organization of tetraspanin-enriched microdomains and to CD81-dependent infection by malaria sporozoites

Olivier Silvie^1,2,*, Stéphanie Charrin^3,4,5,, Martine Billard^3,4,5, Jean-François Franetich^1,2, Krista L. Clark^6,, Geert-Jan van Gemert⁷, Robert W. Sauerwein⁷, François Dautry^4,5,8, Claude Boucheix^3,4,5, Dominique Mazier^1,2 and Eric Rubinstein^3,4,5,*

¹ Inserm, U511, 91 Bd de l'Hôpital, F-75013 Paris, France
² Université Pierre et Marie Curie-Paris 6, Faculté de Médecine Pitié-Salpêtrière, 91 Bd de l'Hôpital, F-75013 Paris, France
³ Inserm, U602, 14 Av Paul Vaillant Couturier, F-94807 Villejuif, France
⁴ Université Paris-Sud 11, 14 Av Paul Vaillant Couturier, F-94807 Villejuif, France
⁵ Institut André Lwoff, IFR 89, 7 rue Guy Môquet, F-94801 Villejuif, France
⁶ Kansas State University, Division of Biology, Manhattan, KS 66506, USA
⁷ University Medical Centre St Radboud, Department of Medical Microbiology, 6500HB Nijmegen, The Netherlands
⁸ CNRS, UPR1983, 7 rue Guy Môquet, F-94801 Villejuif, France

^* Authors for correspondence (e-mail: erubin{at}vjf.inserm.fr; silvie{at}ext.jussieu.fr)

Accepted 1 February 2006

Tetraspanins constitute a family of widely expressed integral membrane proteins that associate extensively with one another and with other membrane proteins to form specific membrane microdomains distinct from conventional lipid rafts. So far, because of the lack of appropriate tools, the functionality of these microdomains has remained largely unknown. Here, using a new monoclonal antibody that only binds to the tetraspanin CD81 associated with other tetraspanins, we show that membrane cholesterol contributes to the organization of tetraspanin microdomains on the surface of live cells. Furthermore, our data demonstrate involvement of host membrane cholesterol during infection by Plasmodium yoelii and Plasmodium falciparum sporozoites, which both depend on host CD81 expression for invasion, but not during CD81-independent infection by Plasmodium berghei sporozoites. Our results unravel a functional link between CD81 and cholesterol during infection by malaria parasites, and illustrate that tetraspanin microdomains constitute a novel type of membrane microdomains that could be used by pathogens for infection.

Key words: Tetraspanins, Microdomains, Cholesterol, Malaria, Plasmodium

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