Potential involvement of kinesin-1 in the regulation of subcellular localization of Girdin
Potential involvement of kinesin-1 in the regulation of subcellular localization of Girdin
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DOI：
10.1016/j.bbrc.2015.06.049
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发表时间：
2015-08-07
影响因子：
3.1
通讯作者：
Takahashi, Masahide
中科院分区：
文献类型：
--
作者：
Muramatsu, Aya;Enomoto, Atsushi;Takahashi, Masahide
Girdin 是一种肌动蛋白结合蛋白，在出生后神经发育和癌症进展中具有多种功能。我们之前表明，Girdin 是出生后脑室下区 (SVZ) 和海马齿状回神经干细胞产生的神经母细胞迁移的调节因子。尽管 Girdin 相互作用蛋白的数量不断增加，但 Girdin 介导的迁移机制尚未完全阐明。 Girdin 与 Disrupted-In-Schizophrenia 1 和partitioning-defected 3 相互作用，这两种蛋白都已被证明与驱动蛋白微管运动蛋白相互作用。基于此，我们发现 Girdin 还与神经元驱动蛋白成员驱动蛋白-1 相互作用。虽然 Girdin 和 kinesin-1 的直接相互作用尚未确定，但有趣的是发现具有富含碱性氨基酸残基区域突变的 Girdin 功能丧失突变小鼠（Basic mut 小鼠）与 kinesin-1 的相互作用有限。此外，具有运动缺陷的 kinesin-1 突变体的表达会导致 Girdin 错误定位。最后，与之前关于驱动蛋白在细胞间粘附分子 N-钙粘蛋白运输中的作用的研究一致，Basic mut 小鼠在迁移的 SVZ 神经母细胞中表现出 N-钙粘蛋白的异常表达模式。这些发现表明 Girdin/kinesin-1 相互作用在调节出生后大脑中神经母细胞迁移中的潜在作用。 (C) 2015 Elsevier Inc. 保留所有权利。
Girdin is an actin-binding protein that has multiple functions in postnatal neural development and cancer progression. We previously showed that Girdin is a regulator of migration for neuroblasts born from neural stem cells in the subventricular zone (SVZ) and the dentate gyrus of the hippocampus in the postnatal brain. Despite a growing list of Girdin-interacting proteins, the mechanism of Girdin-mediated migration has not been fully elucidated. Girdin interacts with Disrupted-In-Schizophrenia 1 and partitioning-defective 3, both of which have been shown to interact with the kinesin microtubule motor proteins. Based on this, we have identified that Girdin also interacts with kinesin-1, a member of neuronal kinesin proteins. Although a direct interaction of Girdin and kinesin-1 has not been determined, it is of interest to find that Girdin loss-of-function mutant mice with the mutation of a basic amino acid residue-rich region (Basic mut mice) exhibit limited interaction with kinesin-1. Furthermore, expression of a kinesin-1 mutant with motor defects, leads to Girdin mislocalization. Finally, consistent with previous studies on the role of kinesin proteins in trafficking a cell-cell adhesion molecule N-cadherin, Basic mut mice showed an aberrant expression pattern of N-cadherin in migrating SVZ neuroblasts. These findings suggest a potential role of Girdin/kinesin-1 interaction in the regulation of neuroblast migration in the postnatal brain. (C) 2015 Elsevier Inc. All rights reserved.