Targeting of the 5-HT1A serotonin receptor to neuronal dendrites is mediated by Yif1B

J Neurosci. 2008 Aug 6;28(32):8063-73. doi: 10.1523/JNEUROSCI.4487-07.2008.


The 5-HT(1A) receptor (5-HT(1A)R) is the most extensively characterized serotonin (5-HT) receptor mainly because of its involvement in the mode of action of antidepressants. The 5-HT(1A)R is confined to the somatodendritic domain of central neurons, where it mediates serotonin-evoked hyperpolarization. Our previous studies underlined the role of the short 5-HT(1A)R C-terminal domain in receptor targeting to dendrites. We used this 17 aa region as bait in a yeast two-hybrid screen, and identified, for the first time, an intracellular protein interacting with the 5-HT(1A)R. This protein is homologous to the yeast Yif1p, previously implicated in vesicular trafficking between the endoplasmic reticulum (ER) and the Golgi apparatus, but not yet characterized in mammals. We confirmed 5-HT(1A)R-Yif1B interaction by glutathione S-transferase pull-down experiments using rat brain extracts and transfected cell lines. Yif1B is highly expressed in the brain, and specifically in raphe 5-HT(1A)R-expressing neurons. Colocalization of Yif1B and 5-HT(1A)R was observed in small vesicles involved in transient intracellular trafficking. Last, inhibition of endogenous expression of Yif1B in primary neuron cultures by small interfering RNA specifically prevented the addressing of 5-HT(1A)R to distal portions of the dendrites, without affecting other receptors, such as sst2A, P2X(2), and 5-HT(3A) receptors. Together, our results provide strong evidence that Yif1B is a member of the ER/Golgi trafficking machinery, which plays a key role in specific targeting of 5-HT(1A)R to the neuronal dendrites. This finding opens up new pathways for the study of 5-HT(1A)R regulation by partner proteins and for the development of novel antidepressant drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • COS Cells
  • Chlorocebus aethiops
  • Dendrites / metabolism*
  • Glutathione Transferase / metabolism
  • LLC-PK1 Cells
  • Male
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology*
  • Neurons / metabolism*
  • Protein Transport / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Serotonin / metabolism
  • Swine
  • Tissue Distribution
  • Transfection
  • Two-Hybrid System Techniques
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism
  • Vesicular Transport Proteins / physiology*


  • Nerve Tissue Proteins
  • Vesicular Transport Proteins
  • Yif1B protein, rat
  • Receptor, Serotonin, 5-HT1A
  • Serotonin
  • Glutathione Transferase