Cell
Volume 158, Issue 6, 11 September 2014, Pages 1335-1347
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Article
Reelin Signaling Specifies the Molecular Identity of the Pyramidal Neuron Distal Dendritic Compartment

https://doi.org/10.1016/j.cell.2014.07.035Get rights and content
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Highlights

  • Reelin signaling specifies the molecular identity of pyramidal neuron tuft dendrites

  • Reelin signaling targets HCN1 and GIRK ion channels to the distal tuft dendrites

  • Reelin signaling creates a pool of active Src family kinases in the distal dendrites

  • Src family kinase activity is critical for the surface expression of HCN1 channels

Summary

The apical dendrites of many neurons contain proximal and distal compartments that receive synaptic inputs from different brain regions. These compartments also contain distinct complements of ion channels that enable the differential processing of their respective synaptic inputs, making them functionally distinct. At present, the molecular mechanisms that specify dendritic compartments are not well understood. Here, we report that the extracellular matrix protein Reelin, acting through its downstream, intracellular Dab1 and Src family tyrosine kinase signaling cascade, is essential for establishing and maintaining the molecular identity of the distal dendritic compartment of cortical pyramidal neurons. We find that Reelin signaling is required for the striking enrichment of HCN1 and GIRK1 channels in the distal tuft dendrites of both hippocampal CA1 and neocortical layer 5 pyramidal neurons, where the channels actively filter inputs targeted to these dendritic domains.

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