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.
Department of Neuroscience, Kavli Institute, College of Physicians and Surgeons, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
Cell. 2014 Sep 11;158(6):1335-1347. doi: 10.1016/j.cell.2014.07.035. Epub 2014 Sep 4.
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.
许多神经元的树突棘包含近端和远端隔室，这些隔室从不同的脑区接收突触输入。这些隔室还包含不同的离子通道，使它们能够对各自的突触输入进行不同的处理，从而使它们具有不同的功能。目前，指定树突棘隔室的分子机制尚不清楚。在这里，我们报告说，细胞外基质蛋白 Reelin 通过其下游的 Dab1 和 Src 家族酪氨酸激酶信号级联反应发挥作用，对于建立和维持皮质锥体神经元远端树突棘隔室的分子特征是必不可少的。我们发现 Reelin 信号对于在海马 CA1 和新皮层 5 层锥体神经元的远端树突丛中 HCN1 和 GIRK1 通道的明显富集是必需的，在这些通道中，这些通道积极地过滤针对这些树突域的输入。
