Transient GPI-anchored protein homodimers are units for raft organization and function

Nat Chem Biol. 2012 Sep;8(9):774-83. doi: 10.1038/nchembio.1028. Epub 2012 Jul 22.


Advanced single-molecule fluorescent imaging was applied to study the dynamic organization of raft-associated glycosylphosphatidylinositol-anchored proteins (GPI-APs) in the plasma membrane and their stimulation-induced changes. In resting cells, virtually all of the GPI-APs are mobile and continually form transient (~200 ms) homodimers (termed homodimer rafts) through ectodomain protein interactions, stabilized by the presence of the GPI-anchoring chain and cholesterol. Heterodimers do not form, suggesting a fundamental role for the specific ectodomain protein interaction. Under higher physiological expression conditions , homodimers coalesce to form hetero- and homo-GPI-AP oligomer rafts through raft-based lipid interactions. When CD59 was ligated, it formed stable oligomer rafts containing up to four CD59 molecules, which triggered intracellular Ca(2+) responses that were dependent on GPI anchorage and cholesterol, suggesting a key part played by transient homodimer rafts. Transient homodimer rafts are most likely one of the basic units for the organization and function of raft domains containing GPI-APs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD59 Antigens / metabolism
  • Dimerization
  • Fluorescence Resonance Energy Transfer
  • Glycosylphosphatidylinositols / metabolism*
  • Membrane Microdomains*


  • CD59 Antigens
  • Glycosylphosphatidylinositols