Map7D2 and Map7D1 facilitate microtubule stabilization through distinct mechanisms in neuronal cells.
Map7D2 and Map7D1 facilitate microtubule stabilization through distinct mechanisms in neuronal cells.
复制标题
DOI：
10.26508/lsa.202201390
复制
发表时间：
2022-08
影响因子：
4.4
通讯作者：
Nakanishi H
中科院分区：
文献类型：
--
作者：
Kikuchi K;Sakamoto Y;Uezu A;Yamamoto H;Ishiguro KI;Shimamura K;Saito T;Hisanaga SI;Nakanishi H
微管相关蛋白Map 7D2和Map 7 D1属于MAP 7家族，通过控制细胞运动和神经突生长的不同机制稳定微管。微管（MT）动力学是通过各种MT相关蛋白（MAP）的协调作用来调节的。然而，MT动力学的调控机制仍不清楚。我们发现，MAP 7家族蛋白Map 7D2稳定MT控制细胞运动和神经突生长。Map 7D2通过其N-末端的一半直接与MT结合，并在体外稳定MT。在小鼠N1-E115神经元细胞中，Map 7D2主要定位于中心体，部分定位于MT上，其表达四个MAP 7家族成员中的两个，Map 7D2和Map 7 D1。Map 7D2损失降低了对MT去稳定剂诺考达唑的抗性，而不影响乙酰化/脱酪氨酸的稳定MT，表明Map 7D2通过直接结合稳定MT。此外，Map 7D2的损失增加了随机细胞迁移和神经突生长的速率，大概是通过扰乱MT稳定和不稳定之间的平衡。Map 7 D1表现出与Map 7D2相似的亚细胞定位和基因敲除表型。然而，与Map 7D2相反，Map 7 D1是维持乙酰化稳定MT所必需的。两者合计，我们的数据表明，Map 7D2和Map 7 D1促进MT稳定通过不同的机制，在细胞运动和轴突生长。
The microtubule-associated proteins Map7D2 and Map7D1, which belong to the MAP7 family, stabilize microtubules through distinct mechanisms for the control of cell motility and neurite outgrowth. Microtubule (MT) dynamics are modulated through the coordinated action of various MT-associated proteins (MAPs). However, the regulatory mechanisms underlying MT dynamics remain unclear. We show that the MAP7 family protein Map7D2 stabilizes MTs to control cell motility and neurite outgrowth. Map7D2 directly bound to MTs through its N-terminal half and stabilized MTs in vitro. Map7D2 localized prominently to the centrosome and partially on MTs in mouse N1-E115 neuronal cells, which expresses two of the four MAP7 family members, Map7D2 and Map7D1. Map7D2 loss decreased the resistance to the MT-destabilizing agent nocodazole without affecting acetylated/detyrosinated stable MTs, suggesting that Map7D2 stabilizes MTs via direct binding. In addition, Map7D2 loss increased the rate of random cell migration and neurite outgrowth, presumably by disturbing the balance between MT stabilization and destabilization. Map7D1 exhibited similar subcellular localization and gene knockdown phenotypes to Map7D2. However, in contrast to Map7D2, Map7D1 was required for the maintenance of acetylated stable MTs. Taken together, our data suggest that Map7D2 and Map7D1 facilitate MT stabilization through distinct mechanisms in cell motility and neurite outgrowth.
登录
查看更多内容
影响因子：
64.8
作者：
Hubbert, C;Guardiola, A;Yao, TP
通讯作者：
Yao, TP
影响因子：
2.9
作者：
Fabre-Jonca, N;Allaman, JM;Masson, D
通讯作者：
Masson, D
影响因子：
8
作者：
Alesi GN;Jin L;Li D;Magliocca KR;Kang Y;Chen ZG;Shin DM;Khuri FR;Kang S
通讯作者：
Kang S
影响因子：
3.3
作者：
Biernat, J;Wu, YZ;Mandelkow, EM
通讯作者：
Mandelkow, EM
影响因子：
5.6
作者：
GASKIN, F;CANTOR, CR;SHELANSKI, ML
通讯作者：
SHELANSKI, ML