Localized sources of neurotrophins initiate axon collateral sprouting

Localized sources of neurotrophins initiate axon collateral sprouting
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DOI:
10.1523/jneurosci.18-14-05403.1998
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发表时间:
1998-07-15
影响因子:
5.3
通讯作者:
Letourneau, PC
Letourneau, PC
中科院分区:
医学1区
文献类型:
--
作者:
Gallo, G;Letourneau, PC

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轴突侧支的萌发在发育和再生过程中神经元连接的建立和完善中是重要的。侧支起源于沿着静止轴突轴的局部丝状伪足活动的出现。我们在这里报告说,感觉神经元轴突轴迅速发芽丝状伪足与神经生长因子包被的聚苯乙烯珠接触的网站。相同的芽可以通过多个珠接触延伸到至少60 μ m。轴突丝状伪足芽往往含有微管,并表现出在珠-轴突接触的站点的轴突微管的解开。细胞松弛素治疗废除了丝状伪足发芽,但没有积累的肌动蛋白丝在网站的珠轴突接触。轴突发芽反应由trkA受体介导,并可能通过磷酸肌醇-3激酶依赖性途径起作用,其方式独立于细胞内Ca 2+波动。这些发现暗示神经营养因子作为直接刺激侧支轴突分支形成的局部线索。
The sprouting of axon collateral branches is important in the establishment and refinement of neuronal connections during both development and regeneration. Collateral branches are initiated by the appearance of localized filopodial activity along quiescent axonal shafts. We report here that sensory neuron axonal shafts rapidly sprout filopodia at sites of contact with nerve growth factor-coated polystyrene beads. Same sprouts can extend up to at least 60 mu m through multiple bead contacts. Axonal filopodial sprouts often contained microtubules and exhibited a debundling of axonal microtubules at the site of bead-axon contact. Cytochalasin treatment abolished the filopodial sprouting, but not the accumulation of actin filaments at sites of bead-axon contact. The axonal sprouting response is mediated by the trkA receptor and likely acts through a phosphoinositide-3 kinase-dependent pathway, in a manner independent of intracellular Ca2+ fluctuations. These findings implicate neurotrophins as local cues that directly stimulate the formation of collateral axon branches.