Temporal-spatial expression and novel biochemical properties of the memory-related protein kibra
Temporal-spatial expression and novel biochemical properties of the memory-related protein kibra
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DOI：
10.1016/j.neuroscience.2008.06.054
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发表时间：
2008-09-09
期刊：
影响因子：
3.3
通讯作者：
Boeckers, T. M.
中科院分区：
文献类型：
--
作者：
Johannsen, S.;Duning, K.;Boeckers, T. M.
哺乳动物大脑储存和回忆信息的能力是基于突触的可塑性，这是由于突触接触的不断重塑。尽管各种各样的蛋白质，如神经递质受体、细胞骨架成分和蛋白激酶已经被确定为记忆形成的调节剂，但它们的具体相互作用和串串仍然知之甚少。KIBRA（肾脑支架蛋白）是记忆相关蛋白激酶C zeta的底物，也是神经元细胞骨架的组成部分，其遗传变异最近被证明与人类记忆表现有关。然而，KIBRA在细胞和生理水平上的功能尚不清楚。为了更深入地了解KIBRA的时空表达，我们对人类和啮齿动物（大鼠）的大脑进行了原位杂交分析和免疫组织学染色。我们的数据表明，KIBRA主要在大脑的记忆相关区域（海马体，皮层）表达，但也在小脑和下丘脑中发现。在海马初级神经元中，KIBRA呈体树突状分布，突触后密度富集。结合研究进一步表明，KIBRA能够形成头尾同源二聚体，二聚化是由内部c2样结构域介导的。我们的数据表明，KIBRA作为连接细胞骨架和信号分子的突触后支架蛋白参与大脑发育和记忆形成。(c) 2008 ibro。Elsevier Ltd.出版。版权所有。
The ability of the mammalian brain to store and recall information is based on synaptic plasticity due to constant remodeling of synaptic contacts. Although various classes of proteins such as neurotransmitter receptors, cytoskeletal components and protein kinases were already identified as modulators of memory formation, their specific interactions and crosstalks are still poorly understood. Genetic variants of the scaffolding protein KIBRA (kidney brain) a substrate of the memory-related protein kinase C zeta and component of the neuronal cytoskeleton, were recently shown to be associated with human memory performance. However, the function of KIBRA on the cellular and physiological level is still unclear.To gain more insights into the temporal and spatial expression of KIBRA, we performed in situ hybridization assays and immunohistological staining of human and rodent (rat) brain. Our data demonstrate that KIBRA is mainly expressed in memory-related regions of the brain (hippocampus, cortex) but is also found in the cerebellum and the hypothalamus. In primary hippocampal neurons, KIBRA displays a somatodendritic distribution and an enrichment at the postsynaptic density. Binding studies further show that KIBRA is able to form head-to-tail homodimers and that dimerization is mediated by the internal C2-like domain. Our data indicate that KIBRA is involved in brain development and memory formation as a postsynaptic scaffold protein connecting cytoskeletal and signaling molecules. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.