Retrograde signaling onto Ret during motor nerve terminal maturation
Retrograde signaling onto Ret during motor nerve terminal maturation
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DOI：
10.1523/jneurosci.4489-07.2008
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发表时间：
2008-01-23
影响因子：
5.3
通讯作者：
Ernfors, Patrik
中科院分区：
文献类型：
--
作者：
Baudet, Christel;Pozas, Ester;Ernfors, Patrik
神经肌肉突触的建立需要神经和肌肉之间的双向信号。虽然对神经释放到肌肉上的信号了解很多，但对神经末梢突触前成熟的重要信号知之甚少。我们的研究结果表明，Ret酪氨酸激酶受体在运动神经元突触中传递信号，有助于运动神经元的存活和突触在出生后阶段的成熟。Ret特异性定位于突触前膜，其配体GDNF（胶质细胞系衍生的神经营养因子）/NTN（neurturin）在骨骼肌组织中表达。在颅运动神经元中条件性地缺乏Ret导致突触前神经肌肉末梢的成熟和特化的发育缺陷。视网膜缺陷的成年舌下神经运动神经元的再生是不受干扰的，但尽管与未受影响的突触后专业化，突触前轴突终末成熟严重受损的情况下，Ret信号。因此，Ret在运动神经末梢中传递信号，所述运动神经末梢在发育期间和在成人的再生期间参与突触前特化的组织和成熟。
Establishment of the neuromuscular synapse requires bidirectional signaling between the nerve and muscle. Although much is known on nerve-released signals onto the muscle, less is known of signals important for presynaptic maturation of the nerve terminal. Our results suggest that the Ret tyrosine kinase receptor transmits a signal in motor neuron synapses that contribute to motor neuron survival and synapse maturation at postnatal stages. Ret is localized specifically to the presynaptic membrane with its ligands, GDNF (glial cell line-derived neurotrophic factor)/NTN (neurturin), expressed in skeletal muscle tissue. Lack of Ret conditionally in cranial motor neurons results in a developmental deficit of maturation and specialization of presynaptic neuromuscular terminals. Regeneration of Ret-deficient adult hypoglossal motor neurons is unperturbed, but despite contact with the unaffected postsynaptic specializations, presynaptic axon terminal maturation is severely compromised in the absence of Ret signaling. Thus, Ret transmits a signal in motor nerve terminals that participate in the organization and maturation of presynaptic specializations during development and during regeneration in the adult.