Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, NY 11794, USA.
Neuron. 2019 Apr 17;102(2):358-372.e9. doi: 10.1016/j.neuron.2019.02.009. Epub 2019 Mar 4.
Among the diverse interneuron subtypes in the neocortex, chandelier cells (ChCs) are the only population that selectively innervate pyramidal neurons (PyNs) at their axon initial segment (AIS), the site of action potential initiation, allowing them to exert powerful control over PyN output. Yet, mechanisms underlying their subcellular innervation of PyN AISs are unknown. To identify molecular determinants of ChC/PyN AIS innervation, we performed an in vivo RNAi screen of PyN-expressed axonal cell adhesion molecules (CAMs) and select Ephs/ephrins. Strikingly, we found the L1 family member L1CAM to be the only molecule required for ChC/PyN AIS innervation. Further, we show that L1CAM is required during both the establishment and maintenance of innervation, and that selective innervation of PyN AISs by ChCs requires AIS anchoring of L1CAM by the cytoskeletal ankyrin-G/βIV-spectrin complex. Thus, our findings identify PyN-expressed L1CAM as a critical CAM required for innervation of neocortical PyN AISs by ChCs. VIDEO ABSTRACT.
在新皮层的各种中间神经元亚型中，叉头盒蛋白细胞（ChCs）是唯一选择性地在其轴突起始段（AIS）支配锥体神经元（PyNs）的细胞，AIS 是动作电位起始的部位，使它们能够对 PyN 输出施加强大的控制。然而，其亚细胞支配 PyN AIS 的机制尚不清楚。为了确定 ChC/PyN AIS 支配的分子决定因素，我们对 PyN 表达的轴突细胞粘附分子（CAMs）和选择 Ephs/ephrins 进行了体内 RNAi 筛选。令人惊讶的是，我们发现 L1 家族成员 L1CAM 是 ChC/PyN AIS 支配所必需的唯一分子。此外，我们表明，L1CAM 在支配的建立和维持过程中都是必需的，并且 ChCs 对 PyN AIS 的选择性支配需要 L1CAM 通过细胞骨架锚蛋白-G/βIV- spectrin 复合物锚定在 AIS 上。因此，我们的发现确定了 PyN 表达的 L1CAM 作为 ChC 支配新皮层 PyN AIS 所必需的关键 CAM。视频摘要。
