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驱动蛋白I马达的缺失揭示了神经营养因子-3对稳态分支控制的一种机制。

Deletion of a kinesin I motor unmasks a mechanism of homeostatic branching control by neurotrophin-3.

作者信息

Auer Thomas O, Xiao Tong, Bercier Valerie, Gebhardt Christoph, Duroure Karine, Concordet Jean-Paul, Wyart Claire, Suster Maximiliano, Kawakami Koichi, Wittbrodt Joachim, Baier Herwig, Del Bene Filippo

机构信息

Institut Curie, Centre de Recherche, Paris, France.

Department of Physiology, University of California San Francisco, San Francisco, United States.

出版信息

Elife. 2015 Jun 15;4:e05061. doi: 10.7554/eLife.05061.

DOI:10.7554/eLife.05061
PMID:26076409
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4467164/
Abstract

Development and function of highly polarized cells such as neurons depend on microtubule-associated intracellular transport, but little is known about contributions of specific molecular motors to the establishment of synaptic connections. In this study, we investigated the function of the Kinesin I heavy chain Kif5aa during retinotectal circuit formation in zebrafish. Targeted disruption of Kif5aa does not affect retinal ganglion cell differentiation, and retinal axons reach their topographically correct targets in the tectum, albeit with a delay. In vivo dynamic imaging showed that anterograde transport of mitochondria is impaired, as is synaptic transmission. Strikingly, disruption of presynaptic activity elicits upregulation of Neurotrophin-3 (Ntf3) in postsynaptic tectal cells. This in turn promotes exuberant branching of retinal axons by signaling through the TrkC receptor (Ntrk3). Thus, our study has uncovered an activity-dependent, retrograde signaling pathway that homeostatically controls axonal branching.

摘要

诸如神经元等高度极化细胞的发育和功能依赖于微管相关的细胞内运输，但对于特定分子马达在突触连接建立过程中的作用却知之甚少。在本研究中，我们调查了驱动蛋白I重链Kif5aa在斑马鱼视网膜顶盖回路形成过程中的功能。对Kif5aa进行靶向破坏并不影响视网膜神经节细胞的分化，并且视网膜轴突虽有延迟，但仍能到达顶盖中其拓扑学上正确的靶点。体内动态成像显示，线粒体的顺向运输受损，突触传递也受到影响。令人惊讶的是，突触前活动的破坏会引发突触后顶盖细胞中神经营养因子3（Ntf3）的上调。这反过来又通过TrkC受体（Ntrk3）发出信号，促进视网膜轴突的过度分支。因此，我们的研究发现了一条依赖于活动的逆行信号通路，该通路以稳态方式控制轴突分支。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d36d/4467164/1f30d65bd493/elife05061fs011.jpg
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