Koh Y H, Popova E, Thomas U, Griffith L C, Budnik V
Department of Biology, University of Massachusetts, Amherst 01003, USA.
Cell. 1999 Aug 6;98(3):353-63. doi: 10.1016/s0092-8674(00)81964-9.
Discs large (DLG) mediates the clustering of synaptic molecules. Here we demonstrate that synaptic localization of DLG itself is regulated by CaMKII. We show that DLG and CaMKII colocalize at synapses and exist in the same protein complex. Constitutively activated CaMKII phenocopied structural abnormalities of dlg mutant synapses and dramatically increased extrajunctional DLG. Decreased CaMKII activity caused opposite alterations. In vitro, CaMKII phosphorylated a DLG fragment with a stoichiometry close to one. Moreover, expression of site-directed dlg mutants that blocked or mimicked phosphorylation had effects similar to those observed upon inhibiting or constitutively activating CaMKII. We propose that CaMKII-dependent DLG phosphorylation regulates the association of DLG with the synaptic complex during development and plasticity, thus providing a link between synaptic activity and structure.
盘状大蛋白(DLG)介导突触分子的聚集。在此我们证明,DLG自身的突触定位受钙/钙调蛋白依赖性蛋白激酶II(CaMKII)调控。我们发现DLG和CaMKII在突触处共定位,并存在于同一蛋白复合物中。组成型激活的CaMKII模拟了dlg突变体突触的结构异常,并显著增加了突触外DLG。CaMKII活性降低则导致相反的变化。在体外,CaMKII使一个DLG片段磷酸化,化学计量比接近1。此外,阻断或模拟磷酸化的定点dlg突变体的表达所产生的效应,与抑制或组成型激活CaMKII时观察到的效应相似。我们提出,CaMKII依赖性的DLG磷酸化在发育和可塑性过程中调节DLG与突触复合物的结合,从而在突触活动和结构之间建立联系。