αvβ5 integrin mediates the effect of vitronectin on the initial stage of differentiation in mouse cerebellar granule cell precursors
αvβ5 integrin mediates the effect of vitronectin on the initial stage of differentiation in mouse cerebellar granule cell precursors
复制标题
DOI：
10.1016/j.brainres.2018.04.025
复制
发表时间：
2018-07-15
期刊：
影响因子：
2.9
通讯作者：
Miyamoto, Yasunori
中科院分区：
文献类型：
--
作者：
Abe, Ayaka;Hashimoto, Kei;Miyamoto, Yasunori
玻连蛋白（Vitronectin，VN）是细胞外基质蛋白之一，通过促进小脑颗粒细胞（CGC）的分化进程来控制CGC的成熟。然而，VN在CGC前体细胞（CGCPs）分化初期的受体尚未明确。在这项研究中，我们的特点是在CGCP的VN受体候选人。首先，我们证实，α v β 3和α v β 5整合素，这是VN的受体候选人，与VN共定位在发育中的小脑和原代培养的CGCP。接下来，用针对每种整联蛋白的小干扰RNA（siRNA）敲低（KD）α v、β 3和β 5整联蛋白降低了Tuj 1（最终分化标志物）阳性CGCP的比率。我们进一步研究了α v β 3和α v β 5整合素是否控制初始分化阶段。α v和β 5整合素的KD，而不是β 3整合素的KD，显著增加了瞬时轴突糖蛋白1（TAG 1），一种初始分化标志物，阳性CGCP的比例，而α v和β 3整合素的KD，而不是β 5整合素，刺激CGCP的增殖。β 5整合素的过表达也刺激了初始分化阶段的进展。为了证实α v β 5整联蛋白和VN之间的相互作用，将VN加入β 5整联蛋白-KD CGCP中。VN对初始分化进程的促进作用被使用小发夹RNA（shRNA）的β 5整合素KD所消除。总之，我们的结果表明，α v β 5整合素，作为VN的受体，是负责在小鼠CGCP的初始分化阶段的进展。(C)2018 Elsevier B. V.版权所有。
Vitronectin (VN), one of the extracellular matrix proteins, controls the maturation of cerebellar granule cells (CGCs) through the promotion of the initial differentiation stage progress. However, the receptors of VN in the initial differentiation stage of CGC precursors (CGCPs) have not been clarified. In this study, we characterized the receptor candidates for VN in CGCPs. First, we confirmed that alpha v beta 3 and alpha v beta 5 integrins, which are receptor candidates for VN, were co-localized with VN in the developing cerebellum and primary cultured CGCPs. Next, the knockdown (KD) of alpha v, beta 3, and beta 5 integrins with small interference RNA (siRNA) for each integrin reduced the ratio of Tuj1, a final differentiation marker, -positive CGCPs. We further studied whether alpha v beta 3 and alpha v beta 5 integrins control the initial differentiation stage. The KD of alpha v and beta 5, but not beta 3, integrins significantly increased the ratio of transient axonal glycoprotein 1 (TAG1), an initial differentiation marker,-positive CGCPs, whereas the KD of alpha v and beta 3 integrins, not beta 5 integrin, stimulated the proliferation of CGCPs. Overexpression of beta 5 integrin stimulated the progress of the initial differentiation stage as well. To confirm the interaction between alpha v beta 5 integrin and VN, VN was added to beta 5 integrin-KD CGCPs. The promotion of the progress of initial differentiation by VN was abrogated by beta 5 integrin KD using small hairpin RNA (shRNA). Taken together, our results indicated that alpha v beta 5 integrin, as the very receptor of VN, is responsible for the progress of the initial differentiation stage in mouse CGCPs. (C) 2018 Elsevier B.V. All rights reserved.