Gangliosides play an important role in the organisation of CD82-enriched microdomains
Résumé
Four transmembrane domain proteins of the tetraspanin superfamily are the organisers of specific microdomains at the membrane (tetraspanin-enriched microdomains or TERM) that incorporate various transmembrane receptors and modulate their activities. The structural aspects of the organisation of TERM are poorly understood. Here we investigated the role of gangliosides in the assembly and stability of TERM. We demonstrated that inhibition of the glycosphingolipid biosynthetic pathway with specific inhibitors of glucosylceramide synthase (NB-DGJ and PPMP) resulted in specific weakening of the interactions involving tetraspanin CD82. Furthermore, ectopic expression of the plasma membrane-bound sialidase Neu3 in mammary epithelial cells also affected stability of the complexes containing CD82: its association with tetraspanin CD151 was decreased but the association with EGFR was enhanced. The destabilization of the CD82-containing complexes upon ganglioside depletion correlated with the re-distribution of the proteins within plasma membrane. Importantly, depletion of gangliosides affected EGF-induced signalling only in the presence of CD82. Taken together our results provide strong evidence that gangliosides play an important role in supporting the integrity of CD82-enriched microdomains. Furthermore, these data demonstrate that the association between different tetraspanins in TERM is controlled by distinct mechanisms and identify Neu3 as a first physiological regulator of the integrity of these microdomains.
Origine : Fichiers produits par l'(les) auteur(s)
Loading...