Zhang Yalan, Helm Jessica S, Senatore Adriano, Spafford J David, Kaczmarek Leonard K, Jonas Elizabeth A
Department of Pharmacology, Section of Endocrinology, Yale School of Medicine, New Haven, Connecticut 06520, USA.
J Neurosci. 2008 Mar 5;28(10):2601-12. doi: 10.1523/JNEUROSCI.4314-07.
Activation of protein kinase C (PKC) potentiates secretion in Aplysia peptidergic neurons, in part by inducing new sites for peptide release at growth cone terminals. The mechanisms by which ion channels are trafficked to such sites are, however, not well understood. We now show that PKC activation rapidly recruits new Ca(V)2 subunits to the plasma membrane, and that recruitment is blocked by latrunculin B, an inhibitor of actin polymerization. In contrast, inhibition of microtubule polymerization selectively prevents the appearance of Ca(V)2 subunits only at the distal edge of the growth cone. In resting neurons, Ca(V)2-containing organelles reside in the central region of growth cones, but are absent from distal lamellipodia. After activation of PKC, these organelles are transported on microtubules to the lamellipodium. The ability to traffic to the most distal sites of channel insertion inside the lamellipodium does, therefore, not require intact actin but requires intact microtubules. Only after activation of PKC do Ca(V)2 channels associate with actin and undergo insertion into the plasma membrane.
蛋白激酶C（PKC）的激活增强了海兔肽能神经元的分泌，部分原因是在生长锥末端诱导了新的肽释放位点。然而，离子通道被运输到这些位点的机制尚不清楚。我们现在表明，PKC激活迅速将新的Ca（V）2亚基招募到质膜，并且这种招募被肌动蛋白聚合抑制剂拉春库林B阻断。相反，微管聚合的抑制仅选择性地阻止Ca（V）2亚基出现在生长锥的远端边缘。在静息神经元中，含有Ca（V）2的细胞器位于生长锥的中心区域，但在远端板状伪足中不存在。PKC激活后，这些细胞器通过微管运输到板状伪足。因此，运输到板状伪足内通道插入最远端位点的能力不需要完整的肌动蛋白，但需要完整的微管。只有在PKC激活后，Ca（V）2通道才与肌动蛋白结合并插入质膜。
