Genetic dissection of TrkB activated signalling pathways required for specific aspects of the taste system.
Genetic dissection of TrkB activated signalling pathways required for specific aspects of the taste system.
复制标题
DOI：
10.1186/1749-8104-9-21
复制
发表时间：
2014-09-26
影响因子：
3.6
通讯作者：
Minichiello L
中科院分区：
文献类型：
--
作者：
Koudelka J;Horn JM;Vatanashevanopakorn C;Minichiello L
神经营养蛋白-4 (NT-4) 和脑源性神经营养因子 (BDNF) 与相同的受体 Ntrk2/TrkB 结合，但在啮齿动物味觉系统的发育中发挥不同的作用。然而，缺乏这些过程背后的机制。在这里，我们在体内证明，TrkB 受体上主要接头蛋白对接位点的单个或组合点突变会影响小鼠味觉发育的特定方面，已知这些方面依赖于 BDNF 或 NT-4。特别是，TrkB-SHC 对接位点发生突变的小鼠在发育早期和后期的味觉神经元存活率均降低，此时存活率分别依赖于 NT-4 和 BDNF。此外，舌神经支配和味蕾形态（这两种 BDNF 依赖性功能）在这些突变体中都发生了改变。相比之下，仅 TrkB-PLCγ 对接位点的突变并不影响味觉神经元的存活。此外，这些突变体对舌头的神经支配被延迟，味觉受体的表达也被改变。我们从基因角度剖析了 TrkB 受体下游激活的通路，这些通路是由两种神经营养素 NT-4 和 BDNF 控制的味觉系统的特定方面所必需的。此外，我们的结果表明，TrkB 还通过不同的信号通路调节特定味觉受体的表达。这些结果增进了我们对味觉系统生物学的了解，味觉系统是生物体与环境关系至关重要的基本感觉系统之一。
Neurotrophin-4 (NT-4) and brain derived neurotrophic factor (BDNF) bind to the same receptor, Ntrk2/TrkB, but play distinct roles in the development of the rodent gustatory system. However, the mechanisms underlying these processes are lacking. Here, we demonstrate, in vivo, that single or combined point mutations in major adaptor protein docking sites on TrkB receptor affect specific aspects of the mouse gustatory development, known to be dependent on BDNF or NT-4. In particular, mice with a mutation in the TrkB-SHC docking site had reduced gustatory neuron survival at both early and later stages of development, when survival is dependent on NT-4 and BDNF, respectively. In addition, lingual innervation and taste bud morphology, both BDNF-dependent functions, were altered in these mutants. In contrast, mutation of the TrkB-PLCγ docking site alone did not affect gustatory neuron survival. Moreover, innervation to the tongue was delayed in these mutants and taste receptor expression was altered. We have genetically dissected pathways activated downstream of the TrkB receptor that are required for specific aspects of the taste system controlled by the two neurotrophins NT-4 and BDNF. In addition, our results indicate that TrkB also regulate the expression of specific taste receptors by distinct signalling pathways. These results advance our knowledge of the biology of the taste system, one of the fundamental sensory systems crucial for an organism to relate to the environment.
登录
查看更多内容
味道神经元由大的TRKB受体依赖性和小型TRKB受体独立的亚群组成。
影响因子：
3.7
作者：
Fei D;Krimm RF
通讯作者：
Krimm RF
影响因子：
2.7
作者：
Patel, Ami V.;Krimm, Robin F.
通讯作者：
Krimm, Robin F.
影响因子：
2.7
作者：
Krimm, RF;Miller, KK;Albers, KM
通讯作者：
Albers, KM
DOI：
10.1002/cne.22400
发表时间：
2010-08-15
期刊：
The Journal of comparative neurology
影响因子：
--
作者：
Patel AV;Huang T;Krimm RF
通讯作者：
Krimm RF
影响因子：
64.5
作者：
Yarmolinsky DA;Zuker CS;Ryba NJ
通讯作者：
Ryba NJ