P2X3 receptor localizes into lipid rafts in neuronal cells

✍ Scribed by Fabrizio Vacca; Susanna Amadio; Giuseppe Sancesario; Giorgio Bernardi; Cinzia Volonté

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 399 KB
• Volume: 76
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.20069

✦ Synopsis

P2X receptors are a family of seven (P2X 1-7 ) cation channels gated by extracellular ATP, widely expressed in neurons and nonneuronal cells. Lipid rafts are cholesterol/sphingolipid-rich membrane domains, involved in many cellular processes, including transmembrane receptor signaling, vesicle traffic, and protein sorting. We provide direct biochemical evidence that P2X 3 receptor localizes into lipid rafts, in primary cultures of cerebellar granule neurons as well as in brain and dorsal root ganglia extracts. We show that P2X 3 exhibits all the characteristics distinctive of a protein associated with lipid rafts. These characteristics include resistance to detergent extraction at 4°C, solubility after extraction of cholesterol from membranes with either saponin or methyl-␤-cyclodextrin, and partitioning to low buoyant density fractions after sucrose gradient centrifugation in both detergent-containing and detergent-free conditions. Furthermore, P2X 3 localizes in raft-containing fractions in transiently transfected SH-SY5Y neuroblastoma cells. The present finding contributes to the characterization of the functional localization of P2X 3 in neurons and provides a novel potential mechanism for correct targeting and dynamic activation of this receptor.