A new vesicular scaffolding complex mediates the G-protein-coupled 5-HT1A receptor targeting to neuronal dendrites

J Neurosci. 2012 Oct 10;32(41):14227-41. doi: 10.1523/JNEUROSCI.6329-11.2012.


Although essential for their neuronal function, the molecular mechanisms underlying the dendritic targeting of serotonin G-protein-coupled receptors are poorly understood. Here, we characterized a Yif1B-dependent vesicular scaffolding complex mediating the intracellular traffic of the rat 5-HT(1A) receptor (5-HT(1A)R) toward dendrites. By combining directed mutagenesis, GST-pull down, and surface plasmon resonance, we identified a tribasic motif in the C-tail of the 5-HT(1A)R on which Yif1B binds directly with high affinity (K(D) ≈ 37 nM). Moreover, we identified Yip1A, Rab6, and Kif5B as new partners of the 5-HT(1A)R/Yif1B complex, and showed that their expression in neurons is also crucial for the dendritic targeting of the 5-HT(1A)R. Live videomicroscopy revealed that 5-HT(1A)R, Yif1B, Yip1A, and Rab6 traffic in vesicles exiting the soma toward the dendritic tree, and also exhibit bidirectional motions, sustaining their role in 5-HT(1A)R dendritic targeting. Hence, we propose a new trafficking pathway model in which Yif1B is the scaffold protein recruiting the 5-HT(1A)R in a complex including Yip1A and Rab6, with Kif5B and dynein as two opposite molecular motors coordinating the traffic of vesicles along dendritic microtubules. This targeting pathway opens new insights for G-protein-coupled receptors trafficking in neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Dendrites / genetics
  • Dendrites / physiology*
  • Gene Targeting / methods
  • Humans
  • Matrix Attachment Regions / genetics
  • Matrix Attachment Regions / physiology*
  • Microtubules / metabolism
  • Microtubules / physiology
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Neurons / metabolism
  • Neurons / physiology*
  • Protein Transport / genetics
  • Protein Transport / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT1A / genetics
  • Receptor, Serotonin, 5-HT1A / physiology*
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Synaptic Vesicles / genetics
  • Synaptic Vesicles / metabolism*
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / physiology*


  • Nerve Tissue Proteins
  • Receptors, G-Protein-Coupled
  • Vesicular Transport Proteins
  • Yif1B protein, rat
  • Receptor, Serotonin, 5-HT1A