XLMR protein related to neurite extension (Xpn/KIAA2022) regulates cell-cell and cell-matrix adhesion and migration
XLMR protein related to neurite extension (Xpn/KIAA2022) regulates cell-cell and cell-matrix adhesion and migration
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DOI：
10.1016/j.neuint.2013.09.011
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发表时间：
2013-11-01
影响因子：
4.2
通讯作者：
Katayama, Taiichi
中科院分区：
文献类型：
--
作者：
Magome, Takuya;Hattori, Tsuyoshi;Katayama, Taiichi
X连锁精神发育迟滞（XLMR）是男性中重度智力残疾的常见原因。与神经突延伸相关的XLMR蛋白（Xpn，也称为KIAA 2022）被认为是人类XLMR的基因。虽然Xpn在发育中的大脑中高度表达，并参与PC 12细胞和神经元中的神经突生长，但对Xpn的功能作用知之甚少。在这里，我们表明，Xpn调节PC 12细胞中的细胞-细胞和细胞-基质粘附和迁移。Xpn敲低分别增强由N-钙粘蛋白和β 1-整合素介导的细胞-细胞和细胞-基质粘附。在Xpn敲低的PC 12细胞中，N-Cadherin和β 1-integrin在mRNA和蛋白水平上的表达显著增加。此外，过表达的Xpn蛋白在PC 12和293 T细胞的细胞核中强烈表达。最后，在PC 12细胞伤口愈合测定中，Xpn的耗尽通过增强N-钙粘蛋白和β 1-整联蛋白表达来扰乱细胞迁移。我们的结论是，Xpn调节细胞与细胞和细胞与基质的粘附和细胞迁移通过调节粘附分子的表达。(C)2013爱思唯尔有限公司保留所有权利。
X-linked mental retardation (XLMR) is a common cause of moderate to severe intellectual disability in males. XLMR protein related to neurite extension (Xpn, also known as KIAA2022) has been implicated as a gene responsible for XLMR in humans. Although Xpn is highly expressed in the developing brain and is involved in neurite outgrowth in PC12 cells and neurons, little is known about the functional role of Xpn. Here, we show that Xpn regulates cell-cell and cell-matrix adhesion and migration in PC12 cells. Xpn knockdown enhanced cell-cell and cell-matrix adhesion mediated by N-cadherin and beta 1-integrin, respectively. N-Cadherin and beta 1-integrin expression at the mRNA and protein levels was significantly increased in Xpn knockdown PC12 cells. Furthermore, overexpressed Xpn protein was strongly expressed in the nuclei of PC12 and 293T cells. Finally, depletion of Xpn perturbed cellular migration by enhancing N-cadherin and beta 1-integrin expression in a PC12 cell wound healing assay. We conclude that Xpn regulates cell-cell and cell-matrix adhesion and cellular migration by regulating the expression of adhesion molecules. (C) 2013 Elsevier Ltd. All rights reserved.