Abu-Elneel Kawther, Ochiishi Tomoyo, Medina Miguel, Remedi Monica, Gastaldi Laura, Caceres Alfredo, Kosik Kenneth S
Neuroscience Research Institute, and Department of Molecular Cellular and Developmental Biology, University of California, Santa Barbara, California 93106, USA.
J Biol Chem. 2008 Nov 21;283(47):32781-91. doi: 10.1074/jbc.M804688200. Epub 2008 Sep 22.
Delta-catenin is a synaptic adherens junction protein pivotally positioned to serve as a signaling sensor and integrator. Expression of delta-catenin induces filopodia-like protrusions in neurons. Here we show that the small GTPases of the Rho family act coordinately as downstream effectors of delta-catenin. A dominant negative Rac prevented delta-catenin-induced protrusions, and Cdc42 activity was dramatically increased by delta-catenin expression. A kinase dead LIMK (LIM kinase) and a mutant Cofilin also prevented delta-catenin-induced protrusions. To link the effects of delta-catenin to a physiological pathway, we noted that (S)-3,5-dihydroxyphenylglycine (DHPG) activation of metabotropic glutamate receptors induced dendritic protrusions that are very similar to those induced by delta-catenin. Furthermore, delta-catenin RNA-mediated interference can block the induction of dendritic protrusions by DHPG. Interestingly, DHPG dissociated PSD-95 and N-cadherin from the delta-catenin complex, increased the association of delta-catenin with Cortactin, and induced the phosphorylation of delta-catenin within the sites that bind to these protein partners.
δ-连环蛋白是一种突触黏附连接蛋白，处于关键位置，可作为信号传感器和整合器。δ-连环蛋白的表达会在神经元中诱导丝状伪足样突起。在此我们表明，Rho家族的小GTP酶作为δ-连环蛋白的下游效应器协同发挥作用。显性负性Rac可阻止δ-连环蛋白诱导的突起，而δ-连环蛋白的表达会显著增加Cdc42的活性。激酶失活的LIMK（LIM激酶）和突变型Cofilin也可阻止δ-连环蛋白诱导的突起。为了将δ-连环蛋白的作用与生理途径联系起来，我们注意到代谢型谷氨酸受体的（S）-3,5-二羟基苯甘氨酸（DHPG）激活会诱导树突状突起，这与δ-连环蛋白诱导的突起非常相似。此外，δ-连环蛋白RNA介导的干扰可阻断DHPG对树突状突起的诱导。有趣的是，DHPG使PSD-95和N-钙黏蛋白从δ-连环蛋白复合物中解离，增加了δ-连环蛋白与皮层肌动蛋白的结合，并在与这些蛋白质伴侣结合的位点内诱导了δ-连环蛋白的磷酸化。
