Les sphingolipides : vecteurs d’agents pathogènes et cause de maladies génétiques

Sphingolipids, vehicle for pathogenic agents and cause of genetic diseases

¹ Département de Pharmacologie, Faculté de Médecine, Université de Montréal, H3C 3J7 Montréal, Québec, Canada
² Laboratoire de Chimie Biologique Appliquée, UMR-INRA 1111, Université Paul Cézanne, 13397 Marseille, France
³ Laboratoire de Physiologie Neurovégétative, UMR CNRS 6153-INRA 1147, Université Paul Cézanne, 13397 Marseille, France

^* jean-pierre.niel@univ.u-3mrs.fr

Résumé

Les sphingolipides (SPL) sont des molécules ubiquitaires indispensables au maintien et au développement des organismes vivants. Ils ne sont pas répartis uniformément le long de la membrane mais regroupés sous forme de microdomaines lipidiques appelés rafts. On a longtemps pensé que les SPL avaient uniquement un rôle structural. On sait maintenant qu’ils jouent aussi un rôle de récepteur et de seconds messagers (intervenant dans des fonctions majeures de la vie cellulaire) et que de nombreuses maladies génétiques (sphingolipidoses) s’expliquent par un dysfonctionnement de leur métabolisme. Après un rappel des propriétés structurales des sphingolipides, cet article fait le point sur les relations entre leur rôle de récepteur et l’entrée d’agents pathogens dans la cellule ainsi que sur les mécanismes pathologiques des sphingolipidoses.

Abstract

Sphingolipids are present in all eukaryotic cells and share a sphingoid base : sphingosine. They were first discovered in 1884 and for a long time they were thought to participate to membrane structure only. Recently it has been established that they are mainly located in particular areas of the membrane called rafts which are signalling platforms. It has also been demonstrated that sphingolipids are receptors and second messengers. They play a crucial role in cellular functioning and are necessary to maintenance and developing of living organisms. However due to their receptor properties, they are also gateway for penetration of pathogenic agents such as virus (Ebola, HIV) or toxins (botulinium, tetanus). These agents first bind to glycosphingolipids or proteins mainly located in rafts. The complex so formed is required for the crossing of the membrane by the pathogenic agent. Sphingolipids metabolism is regulated by numerous enzymes. A failure in the activity of one of them induces an accumulation of sphingolipids known as sphingolipidoses. These are genetic diseases having severe consequences for the survival of the organism. The precise mechanisms of the sphingolipidoses are still mainly unknown which explains why few therapeutic strategies are available. These particular properties of lipids rafts and sphingolipids explain why a growing number of studies in the medical and scientific fields are devoted to them.