Recruitment of actin modifiers to TrkA endosomes governs retrograde NGF signaling and survival.
Recruitment of actin modifiers to TrkA endosomes governs retrograde NGF signaling and survival.
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DOI：
10.1016/j.cell.2011.07.008
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发表时间：
2011-08-05
期刊：
影响因子：
64.5
通讯作者：
Ginty DD
中科院分区：
文献类型：
--
作者：
Harrington AW;St Hillaire C;Zweifel LS;Glebova NO;Philippidou P;Halegoua S;Ginty DD
NGF和NT 3合作支持交感神经元的发育。虽然这两种神经营养因子激活TrkA依赖性轴突延伸，但NGF在促进TrkA内体的逆行运输和逆行存活方面是独特的。在这里，我们报告说，肌动蛋白解聚是必不可少的启动NGF/TrkA内体贩运和Rac 1-cofilin信号模块与TrkA早期内体支持其成熟的逆行运输能力的内体。此外，肌动蛋白调节内体组分不存在于NT 3形成的TrkA内体中，解释了NT 3未能支持逆行TrkA转运和存活。NT 3不能激活Rac 1-GTP-cofilin信号传导可能是由于NT 3/TrkA复合物在TrkA早期内体的酸性环境中的不稳定性质。因此，TrkA内体与肌动蛋白调节蛋白结合，以促进F-肌动蛋白分解，使其成熟为具有运输能力的信号内体。这个过程的差异控制解释了最终目标中的NGF，而不是中间目标中的NT 3，如何支持交感神经元的逆行存活。
NGF and NT3 collaborate to support development of sympathetic neurons. Although both neurotrophins activate TrkA-dependent axonal extension, NGF is unique in its ability to promote retrograde transport of TrkA endosomes and retrograde survival. Here, we report that actin depolymerization is essential for initiation of NGF/TrkA endosome trafficking and that a Rac1–cofilin signaling module associated with TrkA early endosomes supports their maturation to retrograde transport-competent endosomes. Moreover, the actin-regulatory endosomal components are absent from NT3-formed TrkA endosomes, explaining the failure of NT3 to support retrograde TrkA transport and survival. The inability of NT3 to activate Rac1-GTP–cofilin signaling is likely due to the labile nature of NT3/TrkA complexes within the acidic environment of TrkA early endosomes. Thus, TrkA endosomes associate with actin-modulatory proteins to promote F-actin disassembly enabling their maturation into transport-competent signaling endosomes. Differential control of this process explains how NGF in final targets, but not NT3 from intermediate targets, supports retrograde survival of sympathetic neurons.
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DOI：
10.1083/jcb.136.2.375
发表时间：
1997-01-27
期刊：
The Journal of cell biology
影响因子：
--
作者：
Belliveau DJ;Krivko I;Kohn J;Lachance C;Pozniak C;Rusakov D;Kaplan D;Miller FD
通讯作者：
Miller FD
影响因子：
11.4
作者：
DAVIES, AM;MINICHIELLO, L;KLEIN, R
通讯作者：
KLEIN, R
影响因子：
56.9
作者：
Deppmann, Christopher D.;Mihalas, Stefan;Ginty, David D.
通讯作者：
Ginty, David D.
影响因子：
64.5
作者：
Palamidessi, Andrea;Frittoli, Emanuela;Di Fiore, Pier Paolo
通讯作者：
Di Fiore, Pier Paolo
影响因子：
56.9
作者：
LEVIMONTALCINI, R
通讯作者：
LEVIMONTALCINI, R