Lillemeier BF, Pfeiffer JR, Surviladze Z, Wilson BS, Davis MM.
Plasma membrane-associated proteins are clustered into islands attached to the cytoskeleton.
Proc Natl Acad Sci U S A. 2006 Dec 12;103(50):18992-7.
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This paper sets a new double twist to the story of microdomains. Once more we learn that cellular membranes are far from the simplistic model found in most textbooks. What is reported is that there are (a minimum) of three different domains. The predominant one is free of proteins and relatively low in cholesterol. Then there are domains packed with proteins and a little more cholesterol. Thirdly, there are raft domains, rich in proteins and cholesterol. As expected, there is little overlap between raft and non-raft domains, but they lie side by side. To make the story more complex, there is the possibility of several different raft and non-raft domain types. But according to this work, lipids aren't doing the job of separating the protein-containing domains; this would rather be done by the cytoskeleton which abundantly connects to the protein islands.
Why should we need lipid rafts (which are supposed to cluster the proteins) if we can use the cytoskeleton to do that job? There may be some potential pitfalls in trying to answer that question; for example, this EM-based analysis strongly depends on the preparation method, including fixation of the samples. Membranes are very sensitive to such changes and may alter appearance and morphology. More work is needed to answer the question whether the role of lipids, such as cholesterol, in lipid microdomains is limited to altering the functionality of membrane proteins, as this work suggests, or whether they are involved in sorting and separating raft and non-raft proteins into their specific lipid microdomains, as the previous literature suggests.
A big surprise is to actually see what appears to be essentially protein-free domains making up the majority of the plasma membrane. Provided that this is not an artifact induced by the preparation/fixation, one wonders what the heck these are for. They must be important, because they are very plentiful.