Scavenger receptor B1 post-translational modifications in Rett syndrome

• Rett patients have an alterated plasma lipid profile.
• SRB1 (HDL receptor) is low in Rett fibroblasts.
• Rett fibroblasts have high level of HNE with formation of HNE–SRB1 adducts.
• SRB1 is ubiquitinated.

The modulation of the HDL receptor scavenger receptor B1 (SRB1) was evaluated in skin fibroblasts isolated from patients with Rett syndrome (RTT), a genetic form of infantile autism. Patients showed an altered plasma lipid profile, while their skin fibroblasts showed a dramatic reduction in SRB1 (immunogold, Western blot and immunohistochemistry). The decreased SRB1 levels were demonstrated to be the consequence of its binding with 4-hydroxy-2-nonenal (4HNE), a product of lipid peroxidation, and its increased ubiquitination. Our findings show for the first time a loss of SRB1 in RTT cells and its relationship with a chronic oxidative stress status.