Semaphorin3A/PlexinA3 association with the Scribble scaffold for cGMP increase is required for apical dendrite development.
Semaphorin3A/PlexinA3 association with the Scribble scaffold for cGMP increase is required for apical dendrite development.
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DOI：
10.1016/j.celrep.2022.110483
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发表时间：
2022-03-15
期刊：
影响因子：
8.8
通讯作者：
Shelly M
中科院分区：
文献类型：
--
作者：
Szczurkowska J;Guo A;Martin J;Lee SI;Martinez E;Chien CT;Khan TA;Singh R;Dadson D;Tran TS;Pautot S;Shelly M
从双极锥体神经元的主导过程到顶端树突的发展可能是由空间组织的外部线索指导的，这些外部线索作用于局部的内在决定因素。调节根尖树突极化的细胞外信号仍然难以捉摸。我们发现，主导过程和根尖树突的发育是由III类信号蛋白指导的，并由一个局部的cgmp合成复合物介导。与cgmp合成酶可溶性鸟苷酸环化酶（sGC）结合的支架蛋白Scribble也与信号蛋白3a （Sema3A）共受体PlexinA3结合。PlexinA3和Sema3A的缺失或敲低或PlexinA3- scribble关联的破坏可阻止Sema3A介导的cGMP增加，导致根尖树突发育缺陷。这些操纵也损害了两极极性和领导过程的建立。局部cGMP升高或sGC表达可缓解PlexinA3敲低或PlexinA3- scribble复合物破坏的影响。在神经元极化过程中，传导过程和根尖树突的发育是由一个连接Semaphorin线索和cGMP增加的支架指导的。Szczurkowska等人的研究表明，空间定向Sema3A可能通过协同受体PlexinA3，在发育锥体神经元的前沿，协调支架蛋白Scribble上的局部cGMP增加，从而促进主导过程和顶端树突的发育。
The development of the apical dendrite from the leading process of the bipolar pyramidal neuron might be directed by spatially organized extrinsic cues acting on localized intrinsic determinants. The extracellular cues regulating apical dendrite polarization remain elusive. We show that leading process and apical dendrite development are directed by class III Semaphorins and mediated by a localized cGMP-synthesizing complex. The scaffolding protein Scribble that associates with the cGMP-synthesizing enzyme soluble guanylate cyclase (sGC) also associates with the Semaphorin3A (Sema3A) co-receptor PlexinA3. Deletion or knockdown of PlexinA3 and Sema3A or disruption of PlexinA3-Scribble association prevents Sema3A-mediated cGMP increase and causes defects in apical dendrite development. These manipulations also impair bipolar polarity and leading process establishment. Local cGMP elevation or sGC expression rescues the effects of PlexinA3 knockdown or PlexinA3-Scribble complex disruption. During neuronal polarization, leading process and apical dendrite development are directed by a scaffold that links Semaphorin cue to cGMP increase. Szczurkowska et al. show that spatially directed Sema3A may promote development of the leading process and the apical dendrite via the co-receptor PlexinA3 by orchestrating localized cGMP increase on the scaffold protein, Scribble, at the leading edge of developing pyramidal neurons.
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影响因子：
16.2
作者：
Jacobson, C;Schnapp, B;Banker, GA
通讯作者：
Banker, GA
影响因子：
64.5
作者：
KLEIN, R;SMEYNE, RJ;BARBACID, M
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在发育和成年海马形成过程中，闪光蛋白3E及其受体Plexind1的新功能。
影响因子：
4.6
作者：
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通讯作者：
Del Río JA
影响因子：
4.8
作者：
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通讯作者：
Koesling, D
影响因子：
5.3
作者：
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通讯作者：
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