No abstract

Members of the CD36 superfamily of scavenger receptor proteins are important regulators of lipid metabolism and innate immunity. They recognize normal and modified lipoproteins, as well as pathogen-associated molecular patterns. The family consists of three members: SR-BI (which delivers cholesterol to the liver and steroidogenic organs and is a co-receptor for hepatitis C virus), LIMP-2/LGP85 (which mediates lysosomal delivery of β-glucocerebrosidase and serves as a receptor for enterovirus 71 and coxsackieviruses) and CD36 (a fatty-acid transporter and receptor for phagocytosis of effete cells and Plasmodium-infected erythrocytes). Notably, CD36 is also a receptor for modified lipoproteins and β-amyloid, and has been implicated in the pathogenesis of atherosclerosis and of Alzheimer's disease. Despite their prominent roles in health and disease, understanding the function and abnormalities of the CD36 family members has been hampered by the paucity of information about their structure. Here we determine the crystal structure of LIMP-2 and infer, by homology modelling, the structure of SR-BI and CD36. LIMP-2 shows a helical bundle where β-glucocerebrosidase binds, and where ligands are most likely to bind to SR-BI and CD36. Remarkably, the crystal structure also shows the existence of a large cavity that traverses the entire length of the molecule. Mutagenesis of SR-BI indicates that the cavity serves as a tunnel through which cholesterol(esters) are delivered from the bound lipoprotein to the outer leaflet of the plasma membrane. We provide evidence supporting a model whereby lipidic constituents of the ligands attached to the receptor surface are handed off to the membrane through the tunnel, accounting for the selective lipid transfer characteristic of SR-BI and CD36.

Perception of visual stimuli improves with training, but improvements are specific for trained stimuli rendering the development of generic training programs challenging. It remains unknown to which extent training of low-level visual features transfers to high-level visual perception, and whether this is accompanied by neuroplastic changes. The current event-related potential (ERP) study showed that training-induced increased sensitivity to a low-level feature, namely low spatial frequency (LSF), alters neural processing of this feature in high-level visual stimuli. Specifically, neural activity related to face processing (N170), was decreased for low (trained) but not high (untrained) SF content in faces following LSF training. These novel results suggest that: (1) SF discrimination learning transfers from simple stimuli to complex objects; and that (2) training the use of specific SF information affects neural processing of facial information. These findings may open up a new avenue to improve face recognition skills in individuals with atypical SF processing, such as in cataract or Autism Spectrum Disorder (ASD).