Maletic-Savatic M, Koothan T, Malinow R
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
J Neurosci. 1998 Sep 1;18(17):6814-21. doi: 10.1523/JNEUROSCI.18-17-06814.1998.
Calcium-evoked dendritic exocytosis (CEDE), demonstrated in cultured hippocampal neurons, is a novel mechanism that could play a role in synaptic plasticity. A number of forms of neuronal plasticity are thought to be mediated by calcium/calmodulin-dependent protein kinase II (CaMKII). Here, we investigate the role of CaMKII in CEDE. We find that the developmental time course of CEDE parallels the expression of alphaCaMKII, a dominant subunit of CaMKII. An inhibitor of this enzyme, KN-62, blocks CEDE. Furthermore, 7 d in vitro neurons (which normally do not express alphaCaMKII nor show CEDE) can undergo CEDE when infected with a recombinant virus producing alphaCaMKII. Expression of a constitutively active CaMKII produces dendritic exocytosis in the absence of calcium stimulus, and this exocytosis is blocked by nocodazole, an inhibitor of microtubule polymerization that also blocks CEDE. These results indicate that CEDE is mediated by the activation of CaMKII, consistent with the view that CEDE plays a role in synaptic plasticity.
钙诱发的树突状胞吐作用（CEDE），在培养的海马神经元中得到证实，是一种可能在突触可塑性中发挥作用的新机制。多种形式的神经元可塑性被认为是由钙/钙调蛋白依赖性蛋白激酶II（CaMKII）介导的。在此，我们研究CaMKII在CEDE中的作用。我们发现CEDE的发育时间进程与CaMKII的主要亚基αCaMKII的表达平行。该酶的抑制剂KN-62可阻断CEDE。此外，体外培养7天的神经元（通常不表达αCaMKII，也不表现出CEDE）在感染产生αCaMKII的重组病毒时可发生CEDE。组成型活性CaMKII的表达在无钙刺激的情况下产生树突状胞吐作用，并且这种胞吐作用被诺考达唑阻断，诺考达唑是一种微管聚合抑制剂，也能阻断CEDE。这些结果表明CEDE是由CaMKII的激活介导的，这与CEDE在突触可塑性中发挥作用的观点一致。
