Protein tyrosine phosphatase receptor type O inhibits trigeminal axon growth and branching by repressing TrkB and Ret signaling.
Protein tyrosine phosphatase receptor type O inhibits trigeminal axon growth and branching by repressing TrkB and Ret signaling.
复制标题
DOI：
10.1523/jneurosci.4707-12.2013
复制
发表时间：
2013-03-20
期刊：
影响因子：
--
通讯作者：
Klein R
中科院分区：
文献类型：
--
作者：
Gatto G;Dudanova I;Suetterlin P;Davies AM;Drescher U;Bixby JL;Klein R
三叉神经节（TG）的轴突分支在发育过程中呈现出特征性的生长和分支模式。TG神经元的亚群表达不同的生长因子受体，但这些不太可能解释轴突分支的独特模式。内在调节因子可能限制或增强细胞对特定配体的反应，从而有助于轴突生长模式的形成。蛋白酪氨酸磷酸酶受体O型（PTPRO）是鸡中依赖Eph受体的视网膜顶盖发育以及小鼠中部分躯干感觉神经元发育所必需的，它可能是TG神经元发育的一种内在调节因子。在胚胎发生过程中，PTPRO主要在TG内的TrkB⁺和Ret⁺机械感受器中表达。在PTPRO突变小鼠中，部分TG神经元长出更长且更复杂的轴突分支。与对照神经元相比，培养的PTPRO⁻/⁻ TG神经元在对脑源性神经营养因子（BDNF）和胶质细胞源性神经营养因子（GDNF）的反应中表现出增强的轴突生长和分支，这表明PTPRO对BDNF/TrkB和GDNF/Ret信号传导的活性起负调控作用。小鼠PTPRO在视网膜顶盖发育和后肢运动轴突导向中不能调节Eph信号传导，这表明鸡和小鼠的PTPRO具有不同的底物特异性。PTPRO已经进化到以细胞类型特异性的方式精细调节生长因子信号传导，从而增加有限数量的受体酪氨酸激酶信号输出的多样性，以控制发育中的感觉神经元的分支形态。蛋白酪氨酸磷酸酶对Eph受体介导的发育过程的调节在鸡和小鼠之间已经出现分化。
Axonal branches of the trigeminal ganglion (TG) display characteristic growth and arborization patterns during development. Subsets of TG neurons express different receptors for growth factors, but these are unlikely to explain the unique patterns of axonal arborizations. Intrinsic modulators may restrict or enhance cellular responses to specific ligands and thereby contribute to the development of axon growth patterns. Protein tyrosine phosphatase receptor type O (PTPRO) which is required for Eph receptor-dependent retinotectal development in chick and for development of subsets of trunk sensory neurons in mouse, may be such an intrinsic modulator of TG neuron development. PTPRO is expressed mainly in TrkB+ and Ret+ mechanoreceptors within the TG during embryogenesis. In PTPRO mutant mice, subsets of TG neurons grow longer and more elaborate axonal branches. Cultured PTPRO−/− TG neurons display enhanced axonal outgrowth and branching in response to BDNF and GDNF compared to control neurons, indicating that PTPRO negatively controls the activity of BDNF/TrkB and GDNF/Ret signaling. Mouse PTPRO fails to regulate Eph signaling in retinocollicular development and in hindlimb motor axon guidance, suggesting that chick and mouse PTPRO have different substrate specificities. PTPRO has evolved to fine tune growth factor signaling in a cell type specific fashion and to thereby increase the diversity of signaling output of a limited number of receptor tyrosine kinases to control the branch morphology of developing sensory neurons. The regulation of Eph receptor-mediated developmental processes by protein tyrosine phosphatases has diverged between chick and mouse.