Identification of sequence motifs that target neuronal nicotinic receptors to dendrites and axons

Jian Xu, Yongling Zhu, Stephen F. Heinemann*

*Corresponding author for this work

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Neuronal nicotinic acetylcholine receptors (nAChRs) belong to a family of ligand-gated ion channels that play important roles in central and peripheral nervous systems. The subcellular distribution of neuronal nAChRs has important implications for function and is not well understood. Here, we analyzed the targeting of two major types of neuronal nAChRs by expressing epitope-tagged subunits in cultured hippocampal neurons. Surprisingly, the α7 nAChR (α7) and α4/β2 nAChR (α4/β2) displayed distinct patterns of expression, with α7 targeted preferentially to the somatodendritic compartments, whereas α4/β22 was localized to both axonal and dendritic domains. When fused to CD4 or IL2RA (interleukin 2 receptor α subunit) proteins, which are normally distributed ubiquitously, the M3-M4 intracellular loop from the α7 subunit promoted dendritic expression, whereas the homologous M3-M4 loop from the α4 subunit led to surface axonal expression. Systemic screening and alanine substitution further identified a 25-residue leucine motif ([DE]XXXL[LI]) containing an axonal targeting sequence within the α4 loop and a 48-residue dileucine and tyrosine motif (YXXØ) containing a dendritic targeting sequence from the α7 loop. These results provide valuable information in understanding diverse roles of neuronal nAChRs in mediating and modulating synaptic transmission, synaptic plasticity, and nicotine addiction.

Original languageEnglish (US)
Pages (from-to)9780-9793
Number of pages14
JournalJournal of Neuroscience
Volume26
Issue number38
DOIs
StatePublished - Sep 20 2006

Keywords

  • Acetylcholine
  • Axon
  • Dendrite
  • Nicotine
  • Receptor
  • Synapse

ASJC Scopus subject areas

  • Neuroscience(all)

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