HAP1 Is Required for Endocytosis and Signalling of BDNF and Its Receptors in Neurons.
HAP1 Is Required for Endocytosis and Signalling of BDNF and Its Receptors in Neurons.
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DOI：
10.1007/s12035-016-0379-0
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发表时间：
2018-03
影响因子：
5.1
通讯作者：
Zhou XF
中科院分区：
文献类型：
--
作者：
Lim Y;Wu LL;Chen S;Sun Y;Vijayaraj SL;Yang M;Bobrovskaya L;Keating D;Li XJ;Zhou XF
当BDNF与其受体TrkB和p75 NTR结合时，BDNF-受体复合物被内吞并运输到细胞体进行下游信号转导，其在神经元功能中起关键作用。亨廷顿蛋白相关蛋白1（HAP 1）参与囊泡在细胞内的运输，并且还与包括TrkB在内的几种膜蛋白相互作用。虽然已经知道HAP 1在囊泡运输和受体稳定中具有功能，但尚未确定HAP 1是否在BDNF及其受体内吞作用中具有作用。在本研究中，我们发现HAP 1与p75 NTR，TrkB和BDNF，特别是新内吞的BDNF形成相互作用的复合物。BDNF和TrkB内化在HAP 1敲除（KO）皮质神经元中被消除。在BDNF刺激后，TrkB下游信号传导途径如ERK、Akt和PLCγ-1也在HAP 1 KO皮质神经元中受损。在细胞培养物和HAP 1 KO小鼠的小脑中，小脑颗粒细胞的增殖也受损。我们的研究结果表明，HAP 1可能在BDNF及其受体的内吞作用中发挥关键作用，并可能促进神经元的存活和增殖。
When BDNF binds to its receptors, TrkB and p75NTR, the BDNF-receptor complex is endocytosed and trafficked to the cell body for downstream signal transduction, which plays a critical role in neuronal functions. Huntingtin-associated protein 1 (HAP1) is involved in trafficking of vesicles intracellularly and also interacts with several membrane proteins including TrkB. Although it has been known that HAP1 has functions in vesicular trafficking and receptor stabilisation, it is not yet established whether HAP1 has a role in BDNF and its receptor endocytosis. In the present study, we found that HAP1 is in an interacting complex with p75NTR, TrkB and BDNF, especially newly endocytosed BDNF. BDNF and TrkB internalisation is abolished in HAP1 knock-out (KO) cortical neurons. TrkB downstream signalling pathways such as ERK, Akt and PLCγ-1 are also impaired in HAP1 KO cortical neurons upon BDNF stimulation. Proliferation of cerebellar granule cells is also impaired in cell culture and cerebellum of HAP1 KO mice. Our findings suggest that HAP1 may play a key role in BDNF and its receptor endocytosis and may promote neuronal survival and proliferation.
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影响因子：
5.3
作者：
Li, SH;Gutekunst, CA;Li, XJ
通讯作者：
Li, XJ
DOI：
10.1002/neu.10323
发表时间：
2004-02-05
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
Howe, CL;Mobley, WC
通讯作者：
Mobley, WC
影响因子：
3.5
作者：
Engelender, S;Sharp, AH;Ross, CA
通讯作者：
Ross, CA
影响因子：
56.9
作者：
LEVIMONTALCINI, R
通讯作者：
LEVIMONTALCINI, R
DOI：
10.1073/pnas.0401860101
发表时间：
2004-08-24
影响因子：
11.1
作者：
Kittler, JT;Thomas, P;Moss, SJ
通讯作者：
Moss, SJ