Kremerskothen Joachim, Kindler Stefan, Finger Indra, Veltel Stefan, Barnekow Angelika
Department for Experimental Tumorbiology, University Muenster, Badestrasse 9, D-48149 Muenster, Germany.
J Neurochem. 2006 Mar;96(6):1659-66. doi: 10.1111/j.1471-4159.2006.03679.x. Epub 2006 Feb 8.
Synaptic plasticity and memory formation involve remodeling of the postsynaptic cytoskeleton, a process that is in part based on both local translation of dendritic mRNAs and synaptic recruitment of newly synthesized proteins. The postsynaptic component Dendrin that is encoded by a dendritically localized mRNA is thought to modulate the structure of the synaptic cytoskeleton. However, molecular mechanisms that control extrasomatic Dendrin mRNA transport and postsynaptic protein recruitment are unknown. The data presented here reveal that Dendrin interacts with the cytoskeletal components alpha-actinin and Maguk with inverted orientation (MAGI) or synaptic scaffolding molecule (S-SCAM). The latter retains Dendrin in the cytoplasm of mammalian cells and prevents its nuclear import. Furthermore in neurons, postsynaptic clustering of Dendrin requires dendritic targeting of its messenger RNA (mRNA), a process that is mediated by a sequence motif within the 3' untranslated region. In summary our finding suggest that postsynaptic recruitment of Dendrin appears to critically depend on both local protein synthesis and association with the synaptic scaffolding protein MAGI/S-SCAM. Its nuclear localization capacity further points to a function in retrograde signaling from the synapse to the nucleus.
突触可塑性和记忆形成涉及突触后细胞骨架的重塑，这一过程部分基于树突状mRNA的局部翻译和新合成蛋白质的突触募集。由树突状定位的mRNA编码的突触后成分树突蛋白被认为可调节突触细胞骨架的结构。然而，控制胞体外树突蛋白mRNA运输和突触后蛋白募集的分子机制尚不清楚。此处呈现的数据表明，树突蛋白与细胞骨架成分α-辅肌动蛋白以及反向定位的膜相关鸟苷酸激酶（MAGI）或突触支架分子（S-SCAM）相互作用。后者将树突蛋白保留在哺乳动物细胞的细胞质中，并阻止其核输入。此外，在神经元中，树突蛋白的突触后聚集需要其信使RNA（mRNA）的树突靶向，这一过程由3'非翻译区内的一个序列基序介导。总之，我们的发现表明，树突蛋白的突触后募集似乎严重依赖于局部蛋白质合成以及与突触支架蛋白MAGI/S-SCAM的结合。其核定位能力进一步表明其在从突触到细胞核的逆行信号传导中发挥作用。
