Combined kinesin-1 and kinesin-3 activity drives axonal trafficking of TrkB receptors in Rab6 carriers.
Combined kinesin-1 and kinesin-3 activity drives axonal trafficking of TrkB receptors in Rab6 carriers.
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DOI：
10.1016/j.devcel.2021.01.010
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发表时间：
2021-02-22
影响因子：
11.8
通讯作者：
Hoogenraad CC
中科院分区：
文献类型：
--
作者：
Zahavi EE;Hummel JJA;Han Y;Bar C;Stucchi R;Altelaar M;Hoogenraad CC
神经元的功能依赖于神经营养受体在其远端过程中的适当定位。神经营养因子受体Trk家族控制着神经元的存活、分化和重塑，并作为从远端轴突向细胞体运输的逆行信号载体而闻名。然而，驱动Trk受体顺行运输到轴突的机制尚不清楚。采用微流体室室装置和诱导分泌实验，系统研究了TrkB受体沿轴突逆行和顺行转运途径在大鼠海马神经元中的作用。我们发现新合成的TrkB受体通过分泌途径运输，并直接传递到轴突。我们发现这些TrkB载体与Rab6相关并受Rab6调控。此外，轴突结合的TrkB分泌载体的形成以及它们的有效进入和超越近端轴突的顺行运输需要激酶1和激酶3的联合活性。内化TrkB受体被分类用于轴突逆行运输分泌载体的直接运输将TrkB传递到轴突这些载体与Rab6-GTPase结合并依赖于Rab6-GTPase进行运输轴突结合载体的形成和运输依赖于激酶1和激酶3运动神经元将信号受体分布到远端轴突以接收细胞外信息。专注于神经营养受体TrkB， Zahavi等人阐明了细胞内运输途径，使神经元能够通过分泌运输载体将TrkB从其在细胞体的合成位点驱动到远端轴突。
Neurons depend on proper localization of neurotrophic receptors in their distal processes for their function. The Trk family of neurotrophin receptors controls neuronal survival, differentiation, and remodeling and are well known to function as retrograde signal carriers transported from the distal axon toward the cell body. However, the mechanism driving anterograde trafficking of Trk receptors into the axon is not well established. We used microfluidic compartmental devices and inducible secretion assay to systematically investigate the retrograde and anterograde trafficking routes of TrkB receptor along the axon in rat hippocampal neurons. We show that newly synthesized TrkB receptors traffic through the secretory pathway and are directly delivered into axon. We found that these TrkB carriers associate and are regulated by Rab6. Furthermore, the combined activity of kinesin-1 and kinesin-3 is needed for the formation of axon-bound TrkB secretory carriers and their effective entry and processive anterograde transport beyond the proximal axon. Internalized TrkB receptors are sorted for retrograde axonal transport Direct trafficking of secretory carriers delivers TrkB to the axon These carriers associate with and depend on Rab6-GTPase for trafficking Formation and transport of axon-bound carriers depend on kinesin-1 and kinesin-3 motors Neurons distribute signaling receptors to distal axons to receive extracellular information. Focusing on the neurotrophic receptor TrkB, Zahavi et al. elucidate an intracellular trafficking pathway that enables neurons to drive TrkB from its site of synthesis at the cell body, via secretory transport carriers, into the distal axon.
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影响因子：
25
作者：
Hoogenraad, CC;Milstein, AD;Sheng, M
通讯作者：
Sheng, M
选择性rab11转运和中枢神经系统轴突的内在再生能力。
影响因子：
7.7
作者：
Koseki H;Donegá M;Lam BY;Petrova V;van Erp S;Yeo GS;Kwok JC;Ffrench-Constant C;Eva R;Fawcett JW
通讯作者：
Fawcett JW
DOI：
10.1083/jcb.201205070
发表时间：
2012-08-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Jenkins B;Decker H;Bentley M;Luisi J;Banker G
通讯作者：
Banker G
DOI：
10.1073/pnas.1332608100
发表时间：
2003-06-24
影响因子：
11.1
作者：
de Boer, E;Rodriguez, P;Strouboulis, J
通讯作者：
Strouboulis, J
影响因子：
7.8
作者：
Fourriere, Lou;Kasri, Amal;Miserey-Lenkei, Stephanie
通讯作者：
Miserey-Lenkei, Stephanie