LRRTM2 与 Neurexin1 相互作用，调节兴奋性突触形成。
LRRTM2 interacts with Neurexin1 and regulates excitatory synapse formation.
机构信息
Neurobiology Section, Division of Biology, University of California, San Diego, La Jolla, CA 92093, USA.
出版信息
Neuron. 2009 Dec 24;64(6):799-806. doi: 10.1016/j.neuron.2009.12.019.
Abstract
We identify the leucine-rich repeat transmembrane protein LRRTM2 as a key regulator of excitatory synapse development and function. LRRTM2 localizes to excitatory synapses in transfected hippocampal neurons, and shRNA-mediated knockdown of LRRTM2 leads to a decrease in excitatory synapses without affecting inhibitory synapses. LRRTM2 interacts with PSD-95 and regulates surface expression of AMPA receptors, and lentivirus-mediated knockdown of LRRTM2 in vivo decreases the strength of evoked excitatory synaptic currents. Structure-function studies indicate that LRRTM2 induces presynaptic differentiation via the extracellular LRR domain. We identify Neurexin1 as a receptor for LRRTM2 based on affinity chromatography. LRRTM2 binds to both Neurexin 1alpha and Neurexin 1beta, and shRNA-mediated knockdown of Neurexin1 abrogates LRRTM2-induced presynaptic differentiation. These observations indicate that an LRRTM2-Neurexin1 interaction plays a critical role in regulating excitatory synapse development.
摘要
我们鉴定出富含亮氨酸重复跨膜蛋白 LRRTM2 是调节兴奋性突触发育和功能的关键调控因子。LRRTM2 在转染的海马神经元中定位于兴奋性突触，并且 shRNA 介导的 LRRTM2 敲低导致兴奋性突触减少而不影响抑制性突触。LRRTM2 与 PSD-95 相互作用并调节 AMPA 受体的表面表达，并且体内慢病毒介导的 LRRTM2 敲低降低了诱发的兴奋性突触电流的强度。结构功能研究表明，LRRTM2 通过细胞外 LRR 结构域诱导突触前分化。我们基于亲和层析鉴定出 Neurexin1 是 LRRTM2 的受体。LRRTM2 与 Neurexin 1alpha 和 Neurexin 1beta 结合，并且 shRNA 介导的 Neurexin1 敲低消除了 LRRTM2 诱导的突触前分化。这些观察结果表明，LRRTM2-Neurexin1 相互作用在调节兴奋性突触发育中起着关键作用。
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