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

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Abstract
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 β‐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.