Raft-based interactions of gangliosides with a GPI-anchored receptor

Nat Chem Biol. 2016 Jun;12(6):402-10. doi: 10.1038/nchembio.2059. Epub 2016 Apr 4.

Abstract

Gangliosides, glycosphingolipids containing one or more sialic acid(s) in the glyco-chain, are involved in various important physiological and pathological processes in the plasma membrane. However, their exact functions are poorly understood, primarily because of the scarcity of suitable fluorescent ganglioside analogs. Here, we developed methods for systematically synthesizing analogs that behave like their native counterparts in regard to partitioning into raft-related membrane domains or preparations. Single-fluorescent-molecule imaging in the live-cell plasma membrane revealed the clear but transient colocalization and codiffusion of fluorescent ganglioside analogs with a fluorescently labeled glycosylphosphatidylinisotol (GPI)-anchored protein, human CD59, with lifetimes of 12 ms for CD59 monomers, 40 ms for CD59's transient homodimer rafts in quiescent cells, and 48 ms for engaged-CD59-cluster rafts, in cholesterol- and GPI-anchoring-dependent manners. The ganglioside molecules were always mobile in quiescent cells. These results show that gangliosides continually and dynamically exchange between raft domains and the bulk domain, indicating that raft domains are dynamic entities.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD59 Antigens / analysis
  • CD59 Antigens / chemistry*
  • CD59 Antigens / metabolism*
  • Diffusion
  • Fluorescence
  • Gangliosides / analysis
  • Gangliosides / chemistry*
  • Gangliosides / metabolism*
  • Glycosylphosphatidylinositols / metabolism*
  • Humans
  • Membrane Microdomains / chemistry
  • Membrane Microdomains / metabolism*
  • Molecular Conformation
  • Protein Binding
  • Time Factors

Substances

  • CD59 Antigens
  • Gangliosides
  • Glycosylphosphatidylinositols
  • CD59 protein, human

Associated data

  • PubChem-Substance/312524318
  • PubChem-Substance/312524319
  • PubChem-Substance/312524320
  • PubChem-Substance/312524321
  • PubChem-Substance/312524322
  • PubChem-Substance/312524323
  • PubChem-Substance/312524324
  • PubChem-Substance/312524325
  • PubChem-Substance/312524326
  • PubChem-Substance/312524327
  • PubChem-Substance/312524328
  • PubChem-Substance/312524329
  • PubChem-Substance/312524330
  • PubChem-Substance/312524331
  • PubChem-Substance/312524332