Despite high expression levels at the plasma membrane or in intracellular vesicles, tetraspanins remain among the most mysterious transmembrane molecules 20 years after their discovery. Several genetic studies in mammals and invertebrates have demonstrated key physiological roles for some of these tetraspanins, in particular in the immune response, sperm–egg fusion, photoreceptor function and the normal function of certain epithelia. Other studies have highlighted their ability to modulate cell migration and metastasis formation. Their role in the propagation of infectious agents has drawn recent attention, with evidence for HIV budding in tetraspanin-enriched plasma membrane domains. Infection of hepatocytic cells by two major pathogens, the hepatitis C virus and the malaria parasite, also requires the tetraspanin CD81. The function of tetraspanins is thought to be linked to their ability to associate with one another and a wealth of other integral proteins, thereby building up an interacting network or ‘tetraspanin web’. On the basis of the biochemical dissection of the tetraspanin web and recent analysis of the dynamics of some of its constituents, we propose that tetraspanins tightly regulate transient interactions between a variety of molecules and as such favour the efficient assembly of specialized structures upon proper stimulation.
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June 2009
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Review Article|
May 13 2009
Lateral organization of membrane proteins: tetraspanins spin their web
Stéphanie Charrin;
Stéphanie Charrin
*Inserm, U602, F-94807, Villejuif, France
†Université Paris-Sud, Institut André Lwoff, F-94807, Villejuif, France
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François le Naour;
François le Naour
*Inserm, U602, F-94807, Villejuif, France
†Université Paris-Sud, Institut André Lwoff, F-94807, Villejuif, France
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Olivier Silvie;
Olivier Silvie
‡Inserm, U511, F-75013, Paris, France
§Université Pierre et Marie Curie-Paris 6, F-75013, Paris, France
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Pierre-Emmanuel Milhiet;
Pierre-Emmanuel Milhiet
∥Inserm, U554, F-34090, Montpellier, France
¶Université de Montpellier, CNRS, UMR 5048, Centre de Biochimie Structurale, F-34090, Montpellier, France
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Claude Boucheix;
Claude Boucheix
*Inserm, U602, F-94807, Villejuif, France
†Université Paris-Sud, Institut André Lwoff, F-94807, Villejuif, France
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Eric Rubinstein
Eric Rubinstein
1
*Inserm, U602, F-94807, Villejuif, France
†Université Paris-Sud, Institut André Lwoff, F-94807, Villejuif, France
1To whom correspondence should be addressed (email eric.rubinstein@inserm.fr).
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Biochem J (2009) 420 (2): 133–154.
Article history
Received:
December 19 2008
Revision Received:
March 17 2009
Accepted:
March 19 2009
Citation
Stéphanie Charrin, François le Naour, Olivier Silvie, Pierre-Emmanuel Milhiet, Claude Boucheix, Eric Rubinstein; Lateral organization of membrane proteins: tetraspanins spin their web. Biochem J 1 June 2009; 420 (2): 133–154. doi: https://doi.org/10.1042/BJ20082422
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