BMPR-2 gates activity-dependent stabilization of primary dendrites during mitral cell remodeling
BMPR-2 gates activity-dependent stabilization of primary dendrites during mitral cell remodeling
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DOI：
10.1016/j.celrep.2021.109276
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发表时间：
2021-06-22
期刊：
影响因子：
8.8
通讯作者：
Imai, Takeshi
中科院分区：
文献类型：
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作者：
Aihara, Shuhei;Fujimoto, Satoshi;Imai, Takeshi
发育中的神经元最初会形成过多的突起，然后根据分子线索和神经元活动对其进行重塑。嗅球内发育的二尖瓣细胞最初延伸出多个初级树突。然后，它们稳定单个初级树突，同时消除其他树突。然而，选择性树突重塑的机制仍然不清楚。使用基于CRISPR-Cas9的基因敲除筛选结合宫内电穿孔，我们确定BMPR-2是选择性树突稳定的关键调节因子。BMPR-2基因敲除及其挽救实验表明，BMPR-2在没有配体的情况下抑制LIMK，从而允许树突失稳。相反，拮抗剂和激动剂的过度表达表明，配体结合的BMPR-2最有可能通过释放LIMK来稳定树突。利用遗传和FRET成像实验，我们证明了NMDARs通过rac1激活游离LIMK，通过F-肌动蛋白的形成促进树突的稳定。因此，BMP配体的伴随输入和神经元的活动确保了初级树突的选择性稳定。
Developing neurons initially form excessive neurites and then remodel them based on molecular cues and neuronal activity. Developing mitral cells in the olfactory bulb initially extend multiple primary dendrites. They then stabilize single primary dendrites while eliminating others. However, the mechanisms underlying selective dendrite remodeling remain elusive. Using CRISPR-Cas9-based knockout screening combined with in utero electroporation, we identify BMPR-2 as a key regulator for selective dendrite stabilization. Bmpr2 knockout and its rescue experiments show that BMPR-2 inhibits LIMK without ligands and thereby permits dendrite destabilization. In contrast, the overexpression of antagonists and agonists indicates that ligand-bound BMPR-2 stabilizes dendrites, most likely by releasing LIMK. Using genetic and FRET imaging experiments, we demonstrate that free LIMK is activated by NMDARs via Rac1, facilitating dendrite stabilization through F-actin formation. Thus, the selective stabilization of primary dendrites is ensured by concomitant inputs of BMP ligands and neuronal activity.