Kinetics of G-protein-coupled receptor endosomal trafficking pathways revealed by single quantum dots

Katye M. Fichter, Marc Flajolet, Paul Greengard, Tania Q. Vu

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

G-protein-coupled receptors (GPCRs) are the largest protein superfamily in the human genome; they comprise 30% of current drug targets and regulate diverse cellular signaling responses. The role of endosomal trafficking in GPCR signaling regulation is gaining substantial consideration. However, this process remains difficult to study due to the inability to distinguish among many individual receptors, simultaneously trafficking within multiple endosomal pathways. Here we show accurate measurement of the internalization and endosomal trafficking of single groups of serotonin (5-hydroxytryptamine, 5-HT) receptors using single quantum dot (QD) probes and quantitative colocalization. We demonstrate that the presence of a QD tag does not interfere with 5-HT receptor internalization or endosomal recycling. Direct measurements show simultaneous trafficking of the 5-HT1A receptor in two distinct endosomal recycling pathways. Single-molecule imaging of endosomal trafficking will significantly impact the understanding of cellular signaling and provide powerful tools to elucidate the actions of GPCR-targeted therapeutics.

Original languageEnglish (US)
Pages (from-to)18658-18663
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number43
DOIs
StatePublished - Oct 26 2010

Keywords

  • Endocytosis
  • Endosome
  • Nanoparticle
  • Serotonin
  • Single-molecule imaging

ASJC Scopus subject areas

  • General

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