National Center for Behavioral Genomics and Volen Center for Complex Systems, Brandeis University, Waltham, Massachusetts 02454, USA.
J Neurosci. 2013 Apr 10;33(15):6504-15. doi: 10.1523/JNEUROSCI.3861-12.2013.
The morphogenesis of the dendritic arbor is a critical aspect of neuronal development, ensuring that proper neural networks are formed. However, the molecular mechanisms that underlie this dendritic remodeling remain obscure. We previously established the activity-regulated GTPase Rem2 as a negative regulator of dendritic complexity. In this study, we identify a signaling pathway whereby Rem2 regulates dendritic arborization through interactions with Ca(2+)/calmodulin-dependent kinases (CaMKs) in rat hippocampal neurons. Specifically, we demonstrate that Rem2 functions downstream of CaMKII but upstream of CaMKIV in a pathway that restricts dendritic complexity. Furthermore, we show that Rem2 is a novel substrate of CaMKII and that phosphorylation of Rem2 by CaMKII regulates Rem2 function and subcellular localization. Overall, our results describe a unique signal transduction network through which Rem2 and CaMKs function to restrict dendritic complexity.
树突分支的形态发生是神经元发育的一个关键方面，确保了适当的神经网络的形成。然而，支持这种树突重塑的分子机制仍不清楚。我们之前确定活性调节 GTPase Rem2 是树突复杂性的负调节剂。在这项研究中，我们确定了一条信号通路，通过该通路，Rem2 通过与大鼠海马神经元中的 Ca(2+)/钙调蛋白依赖性激酶（CaMKs）相互作用来调节树突分支。具体来说，我们证明 Rem2 在 CaMKIV 的上游但在 CaMKII 的下游发挥作用，在该通路中限制树突复杂性。此外，我们表明 Rem2 是 CaMKII 的一个新底物，CaMKII 对 Rem2 的磷酸化调节 Rem2 的功能和亚细胞定位。总的来说，我们的结果描述了一个独特的信号转导网络，通过该网络，Rem2 和 CaMKs 发挥作用以限制树突复杂性。
