Centrosome-dependent microtubule modifications set the conditions for axon formation.
Centrosome-dependent microtubule modifications set the conditions for axon formation.
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DOI：
10.1016/j.celrep.2022.110686
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发表时间：
2022-04-19
期刊：
影响因子：
8.8
通讯作者：
de Anda, Froylan Calderon
中科院分区：
文献类型：
--
作者：
Meka, Durga Praveen;Kobler, Oliver;Hong, Shuai;Friedrich, Carina Meta;Wuesthoff, Souhaila;Henis, Melad;Schwanke, Birgit;Krisp, Christoph;Schmuelling, Nessa;Rueter, Rene;Ruecker, Tabitha;Betleja, Ewelina;Cheng, Tao;Mahjoub, Moe R.;Soba, Peter;Schluter, Hartmut;Fornasiero, Eugenio F.;de Anda, Froylan Calderon
微管（MT）的修饰在轴突发育过程中是至关重要的，稳定的MT填充轴突。这些修饰是如何在空间上协调的尚不清楚。在这里，通过高分辨率显微镜，我们发现，早期发育的神经元有较少的体细胞乙酰化MT限制在中心体附近。然而，在后期，乙酰化的MT在索马中扩散并集中在生长的轴突中。在早期铺板的MT加端蛋白EB 3的神经元中的实时成像显示MTOC附近的位移和生长速率增加，这表明可能支持轴突选择的局部差异。此外，与后期阶段不同，早期发育神经元中的F-肌动蛋白破坏（体细胞乙酰化MT较少）不会诱导多个轴突。中心体蛋白120（Cep 120），促进MT乙酰化/稳定的过表达，诱导多个轴突，而它的敲低下调调节MT动力学和稳定性的蛋白质，阻碍轴突形成。总的来说，我们展示了中心体依赖的MT修饰如何促进轴突形成。Meka等人表明，Cep 120依赖性微管乙酰化在第1阶段集中在中心体，在第2阶段从索马扩散到神经突中，并最终在第3阶段富集在最长的神经突（轴突）中。其他微管蛋白修饰（多聚谷氨酰化、酪氨酸化）或α-微管蛋白本身在对称性破坏期间不遵循逐渐分布。
Microtubule (MT) modifications are critical during axon development, with stable MTs populating the axon. How these modifications are spatially coordinated is unclear. Here, via high-resolution microscopy, we show that early developing neurons have fewer somatic acetylated MTs restricted near the centrosome. At later stages, however, acetylated MTs spread out in soma and concentrate in growing axon. Live imaging in early plated neurons of the MT plus-end protein, EB3, show increased displacement and growth rate near the MTOC, suggesting local differences that might support axon selection. Moreover, F-actin disruption in early developing neurons, which show fewer somatic acetylated MTs, does not induce multiple axons, unlike later stages. Overexpression of centrosomal protein 120 (Cep120), which promotes MT acetylation/stabilization, induces multiple axons, while its knockdown downregulates proteins modulating MT dynamics and stability, hampering axon formation. Collectively, we show how centrosome-dependent MT modifications contribute to axon formation. Meka et al. show that Cep120-dependent microtubule acetylation, concentrated at the centrosome at stage 1, spreads from the soma into neurites at stage 2 and is eventually enriched in the longest neurite (axon) at stage 3. Other tubulin modifications (polyglutamylation, tyrosination) or α-tubulin itself did not follow the gradual distribution during symmetry breakage.
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影响因子：
2.5
作者：
Guha S;Patil A;Muralidharan H;Baas PW
通讯作者：
Baas PW
细胞质动力蛋白在微管和神经丝的轴突转运中的作用。
DOI：
10.1083/jcb.200407191
发表时间：
2005-02-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
He Y;Francis F;Myers KA;Yu W;Black MM;Baas PW
通讯作者：
Baas PW
Aurora在有丝分裂中依赖于中心体依赖的微管组装需要TACC3/Maskin的磷酸化。
影响因子：
7.8
作者：
Kinoshita, Kazuhisa;Noetzel, Tim L;Pelletier, Laurence;Mechtler, Karl;Drechsel, David N;Schwager, Anne;Lee, Mike;Raff, Jordan W;Hyman, Anthony A
通讯作者：
Hyman, Anthony A
影响因子：
16.2
作者：
Jacobson, C;Schnapp, B;Banker, GA
通讯作者：
Banker, GA
影响因子：
8.8
作者：
Joseph, Nimesh;Ai-Jassar, Caezar;van Breugel, Mark
通讯作者：
van Breugel, Mark