Of proneurotrophins and their antineurotrophic effects.
Of proneurotrophins and their antineurotrophic effects.
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DOI：
10.1126/scisignal.2003824
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发表时间：
2013-02-12
影响因子：
7.3
通讯作者：
Giniger E
中科院分区：
文献类型：
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作者：
Kotlyanskaya L;McLinden KA;Giniger E
神经营养因子在整个神经发育过程中起着至关重要的作用。它们通过Trk受体蛋白传递信号，通常与“低亲和力”的p75NTR泛神经营养素共受体有关。神经营养因子被合成为原蛋白；原结构域被蛋白水解性去除，以产生成熟的、可能具有功能的神经营养因子形式。然而，最近的发现揭示了前神经营养素本身的积极作用。在缺少Trks的情况下，原蛋白与p75NTR泛神经营养素受体高度结合，启动一系列独立的信号级联反应，积极对抗成熟生长因子的影响。这些实验表明，前神经营养因子和成熟神经营养因子之间的平衡在调节下游信号方面起着关键作用。这一观点极大地改变了神经营养素领域，也指向了更广泛的观点，即前体蛋白的潜在活性值得更仔细地研究。
Neurotrophins perform essential processes throughout neural development. They signal through Trk receptor proteins, typically in association with a “low affinity” p75NTR pan-neurotrophin co-receptor. Neurotrophins are synthesized as proproteins; the pro domains are removed proteolytically to yield the mature, presumably functional forms of the neurotrophins. Recent findings, however, have revealed a positive role for the proneurotrophins themselves. The proproteins bind with high affinity to the p75NTR pan-neurotrophin receptor in the absence of Trks to initiate a separate set of signaling cascades that actively oppose the effects of the mature growth factors. These experiments suggest that the balance between pro- and mature neurotrophin plays a critical role in tuning downstream signaling. This view changes the neurotrophin field substantially, and also points to the broader idea that the potential activities of precursor proteins deserve a closer look.