title: Reelin signaling specifies the molecular identity of the pyramidal neuron distal dendritic compartment.
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.
authors.affiliation: 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.
authors.forename: Justine V
authors.initials: JV
authors.lastname: Kupferman
authors.affiliation: Department of Neuroscience, Kavli Institute, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Jayeeta
authors.initials: J
authors.lastname: Basu
authors.affiliation: Department of Neuroscience, Kavli Institute, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Marco J
authors.initials: MJ
authors.lastname: Russo
authors.affiliation: Department of Biology, Kavli Institute, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Jenieve
authors.initials: J
authors.lastname: Guevarra
authors.affiliation: Department of Neuroscience, Kavli Institute, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
authors.forename: Stephanie K
authors.initials: SK
authors.lastname: Cheung
authors.affiliation: 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.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Siegelbaum
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006624:Hippocampus / Q000378:metabolism; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C103773:Dab1 protein, mouse; D016326:Extracellular Matrix Proteins; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C578666:Hcn1 protein, mouse; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D000091042:Reelin Protein; D019061:src-Family Kinases; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases