Native clusters (black circles) reorganize (red circles) after cross-linking removes one type of GPI-AP.

Mayor/Elsevier

Native clusters (black circles) reorganize (red circles) after cross-linking removes one type of GPI-AP.

Mayor/Elsevier

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Tiny but dynamic domains define the elusive lipid raft, based on results from Madan Rao, Satyajit Mayor (National Centre for Biological Science, Bangalore, India), and colleagues.

Describing the structure and components of rafts—membrane domains enriched in specific lipids and proteins—has been a long-standing challenge for cell biologists. In this new report, the authors use FRET, photobleaching, and theoretical modeling to get the closest look yet at raft components called GPI-APs (GPI-anchored proteins). They show that lipid rafts contain small clusters (four or fewer molecules) of very tight-knit GPI-APs packed into an ∼4-nm-wide space.

About a third of any given GPI-AP species is found in rafts. The rest remain as monomers. This percentage holds true across multiple expression levels, which is inconsistent with equilibrium-based formation. “It means rafts have to be actively maintained,” says Mayor. “And within these regions, the GPI proteins form clusters.”

Different types of GPI-APs are found within a cluster, and the clusters are dynamic—cross-linking of one species removes it from the cluster, and another species readily takes its place. The cross-linked GPI-APs formed larger groups that were endocytosed by the clathrin-mediated pathway, rather than the route responsible for uptake of raft GPI-APs. Thus, ligation of a receptor could change its fate by altering its lipid environment. ▪

Reference:

Sharma, P., et al.
2004
.
Cell.
116
:
577
–589.