Interaction and localization of Necl-5 and PDGF receptor β at the leading edges of moving NIH3T3 cells:: Implications for directional cell movement
Interaction and localization of Necl-5 and PDGF receptor β at the leading edges of moving NIH3T3 cells:: Implications for directional cell movement
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DOI：
10.1111/j.1365-2443.2008.01167.x
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发表时间：
2008-03-01
期刊：
影响因子：
2.1
通讯作者：
Takai, Yoshimi
中科院分区：
文献类型：
--
作者：
Amano, Hisayuki;Ikeda, Wataru;Takai, Yoshimi
以前的研究表明，血小板衍生生长因子（PDGF）受体在物理和功能上与整合素α（v）β（3）相互作用，有效地诱导细胞运动。我们先前表明，最初被鉴定为脊髓灰质炎病毒受体的Necl-5与整合素α（v）β（3）相互作用，并增强其聚集和在运动细胞前缘形成焦点复合物，从而增强细胞运动。我们在此表明，Necl-5还与NIH 3 T3细胞中的PDGF受体相互作用，并调节PDGF受体与整合素α（v）β（3）之间的相互作用，有效诱导定向细胞运动。PDGF受体与Necl-5和整联蛋白α（v）β（3）共定位于板状伪足上的外周皱褶处，其响应于PDGF而在运动细胞的前缘处形成，但不在这些皱褶下的焦点复合物处，而Necl-5和整联蛋白α（v）β（3）共定位于这些焦点复合物处。这三种分子在外周皱褶处的聚集需要玻连蛋白激活整合素α（v）β（3），以及PDGF诱导的小G蛋白Rac激活和随后的肌动蛋白细胞骨架重组。这些结果表明Necl-5通过与整合素α（v）β（3）和PDGF受体两者物理和功能相互作用而在定向细胞运动中起关键作用。
It was previously shown that platelet-derived growth factor (PDGF) receptor physically and functionally interacts with integrin alpha(v)beta(3), effectively inducing cell movement. We previously showed that Necl-5, originally identified as a poliovirus receptor, interacts with integrin alpha(v)beta(3) and enhances its clustering and the formation of focal complexes at the leading edges of moving cells, resulting in an enhancement of cell movement. We showed here that Necl-5 additionally interacts with PDGF receptor in NIH3T3 cells and regulates the interaction between PDGF receptor and integrin alpha(v)beta(3), effectively inducing directional cell movement. PDGF receptor co-localized with Necl-5 and integrin alpha(v)beta(3) at peripheral ruffles over lamellipodia, which were formed at the leading edges of moving cells in response to PDGF, but not at the focal complexes under these ruffles, whereas Necl-5 and integrin alpha(v)beta(3) co-localized at these focal complexes. The clustering of these three molecules at peripheral ruffles required the activation of integrin alpha(v)beta(3) by vitronectin and the PDGF-induced activation of the small G protein Rac and subsequent re-organization of the actin cytoskeleton. These results indicate a key role of Necl-5 in directional cell movement by physically and functionally interacting with both integrin alpha(v)beta(3) and PDGF receptor.