A cytoplasmic motif targets neuroligin-1 exclusively to dendrites of cultured hippocampal neurons

Eur J Neurosci. 2005 Nov;22(9):2381-6. doi: 10.1111/j.1460-9568.2005.04400.x.


The formation of neuronal synapses is thought to depend on trans-synaptic interactions between cell adhesion molecules (CAMs) on the surface of axons and dendrites. Synapses are highly asymmetric structures. Pre- and post-synaptic domains might therefore be assembled around heterophilic CAMs which are polarized to axons vs. dendrites. We here investigated the targeting of neuroligin (NLG)-1, a heterophilic CAM, which promotes synapse formation through interaction with its receptor beta-neurexin in axons. We demonstrate that NLG-1 is highly polarized to the dendritic plasma membrane. Dendritic targeting relies on a cytoplasmic amino acid motif. By expressing chimeras of NLG-1 and CD8, an unpolarized protein, we show that the cytoplasmic domain of NLG-1 is necessary and sufficient for dendritic targeting. Furthermore, by truncation analysis we isolated a 32-amino-acid targeting motif. When appended to CD8 this cytoplasmic sequence is sufficient to direct exclusively dendritic localization of the protein. Analysis of yellow fluorescent protein-tagged NLG-1 revealed that vesicular structures containing NLG-1 are excluded from the axon indicating that polarized distribution may be achieved by direct dendritic transport. We propose that the strict polarity of NLG-1 contributes to the directional assembly of synapses during development of the central nervous system.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / metabolism
  • CD8 Antigens / metabolism
  • Cell Adhesion Molecules, Neuronal
  • Cells, Cultured
  • Cytoplasm / metabolism*
  • Dendrites / metabolism*
  • Embryo, Mammalian
  • Green Fluorescent Proteins / metabolism
  • Hippocampus / cytology*
  • Luminescent Proteins / metabolism
  • Membrane Proteins / metabolism*
  • Microtubule-Associated Proteins / metabolism
  • Mutagenesis / physiology
  • Nerve Tissue Proteins / metabolism*
  • Neurons / cytology*
  • Protein Structure, Tertiary
  • Rats
  • Transfection / methods


  • Bacterial Proteins
  • CD8 Antigens
  • Cell Adhesion Molecules, Neuronal
  • Luminescent Proteins
  • MAP2 protein, rat
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • neuroligin 1
  • yellow fluorescent protein, Bacteria
  • Green Fluorescent Proteins