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首页> 外文期刊>Cell discovery. >Selected SNARE proteins are essential for the polarized membrane insertion of igf-1 receptor and the regulation of initial axonal outgrowth in neurons
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Selected SNARE proteins are essential for the polarized membrane insertion of igf-1 receptor and the regulation of initial axonal outgrowth in neurons

机译：选定的SNARE蛋白对于igf-1受体的极化膜插入和神经元的初始轴突生长的调节至关重要

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The establishment of polarity necessitates initial axonal outgrowth and, therefore, the addition of new membrane to the axon’s plasmalemma. Axolemmal expansion occurs by exocytosis of plasmalemmal precursor vesicles (PPVs) primarily at the neuronal growth cone. Little is known about the SNAREs family proteins involved in the regulation of PPV fusion with the neuronal plasmalemma at early stages of differentiation. We show here that five SNARE proteins (VAMP2, VAMP4, VAMP7, Syntaxin6 and SNAP23) were expressed by hippocampal pyramidal neurons before polarization. Expression silencing of three of these proteins (VAMP4, Syntaxin6 and SNAP23) repressed axonal outgrowth and the establishment of neuronal polarity, by inhibiting IGF-1 receptor exocytotic polarized insertion, necessary for neuronal polarization. In addition, stimulation with IGF-1 triggered the association of VAMP4, Syntaxin6 and SNAP23 to vesicular structures carrying the IGF-1 receptor and overexpression of a negative dominant form of Syntaxin6 significantly inhibited exocytosis of IGF-1 receptor containing vesicles at the neuronal growth cone. Taken together, our results indicated that VAMP4, Syntaxin6 and SNAP23 functions are essential for regulation of PPV exocytosis and the polarized insertion of IGF-1 receptor and, therefore, required for initial axonal elongation and the establishment of neuronal polarity.
机译：极性的建立需要最初的轴突生长，因此，需要在轴突的浆膜中添加新的膜。轴突膨胀主要通过在神经元生长锥处的质膜前体囊泡（PPV）胞吐而发生。 SNAREs家族蛋白在分化的早期阶段与PPV与神经质浆膜融合的调节有关的了解甚少。我们在这里显示了五种SNARE蛋白（VAMP2，VAMP4，VAMP7，Syntaxin6和SNAP23）在极化之前由海马锥体神经元表达。这些蛋白中的三种（VAMP4，Syntaxin6和SNAP23）的表达沉默通过抑制IGF-1受体胞外极化插入而抑制了轴突的生长和神经元极性的建立，这对于神经元极化是必需的。另外，用IGF-1刺激触发了VAMP4，Syntaxin6和SNAP23与携带IGF-1受体的囊泡结构的缔合，并且Syntaxin6负显性形式的过表达显着抑制了神经元生长锥处含有IGF-1受体的囊泡的胞吐作用。 。两者合计，我们的结果表明，VAMP4，Syntaxin6和SNAP23功能对于调节PPV胞吐作用和IGF-1受体的极化插入至关重要，因此是初始轴突伸长和神经元极性建立所必需的。

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