Reelin signaling specifies the molecular identity of the pyramidal neuron distal dendritic compartment

Justine V Kupferman; Jayeeta Basu; Marco J Russo; Jenieve Guevarra; Stephanie K Cheung; Steven A Siegelbaum

doi:10.1016/j.cell.2014.07.035

Reelin signaling specifies the molecular identity of the pyramidal neuron distal dendritic compartment

Cell. 2014 Sep 11;158(6):1335-1347. doi: 10.1016/j.cell.2014.07.035. Epub 2014 Sep 4.

Authors

Justine V Kupferman¹, Jayeeta Basu², Marco J Russo², Jenieve Guevarra³, Stephanie K Cheung², Steven A Siegelbaum⁴

Affiliations

¹ Department of Biology, Kavli Institute, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA; Department of Neuroscience, Kavli Institute, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
² Department of Neuroscience, Kavli Institute, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
³ Department of Biology, Kavli Institute, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
⁴ Department of Neuroscience, Kavli Institute, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA; Department of Pharmacology, Kavli Institute, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA; Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA. Electronic address: sas8@columbia.edu.

Abstract

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.

Publication types

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

MeSH terms

Animals
Cell Adhesion Molecules, Neuronal / genetics
Cell Adhesion Molecules, Neuronal / metabolism*
Dendrites / metabolism*
Extracellular Matrix Proteins / genetics
Extracellular Matrix Proteins / metabolism*
G Protein-Coupled Inwardly-Rectifying Potassium Channels / metabolism
Gene Knockdown Techniques
Hippocampus / metabolism
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / genetics
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / metabolism
Mice
Mice, Inbred C57BL
Mice, Neurologic Mutants
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism*
Neurons / metabolism*
Potassium Channels / genetics
Potassium Channels / metabolism
Reelin Protein
Serine Endopeptidases / genetics
Serine Endopeptidases / metabolism*
Signal Transduction
src-Family Kinases / metabolism

Substances

Cell Adhesion Molecules, Neuronal
Dab1 protein, mouse
Extracellular Matrix Proteins
G Protein-Coupled Inwardly-Rectifying Potassium Channels
Hcn1 protein, mouse
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
Nerve Tissue Proteins
Potassium Channels
Reelin Protein
src-Family Kinases
Reln protein, mouse
Serine Endopeptidases

Abstract

Publication types

MeSH terms

Substances

Grants and funding