An MBoC Favorite: Gangliosides GM1 and GM3 in the living cell membrane form clusters susceptible to cholesterol depletion and chilling

In celebration of MBoC’s first 20 years, members of the Editorial Board, members of the ASCB Council, and others comment on their favorite MBoC papers from the past two decades. This article is the MBoC paper most cited by my group, and so it is clearly our MBoC favorite. The authors revived an electron microscopy technique in which membrane molecules fixed on the platinum replicas of quickly frozen and freeze-fractured specimens were immunogold labeled and applied this technique to observe the two-dimensional distribution of gangliosides GM1 and GM3, putative raft molecules in the plasma membrane. The authors were the first to show that GM1 and GM3 form cholesterol-dependent clusters (GM1 cluster size <100 nm) and that these clusters do not coincide. These results indicate the presence of various raft domains with different compositions and the mechanisms for assembling the same species of gangliosides. They were, and still are, exciting data for scientists interested in raft domains, because they clearly indicate that molecule-specific, homophilic interactions, in addition to more general, cholesterol-dependent raft-lipid interactions, are required for generating certain raft domains in the plasma membrane. This work changed the concept of raft domains.