Leader cell PLCγ1 activation during keratinocyte collective migration is induced by EGFR localization and clustering.
Leader cell PLCγ1 activation during keratinocyte collective migration is induced by EGFR localization and clustering.
复制标题
角质形成细胞集体迁移过程中前导细胞 PLCγ1 激活是由 EGFR 定位和聚集诱导的。
DOI：
10.1002/btm2.10138
复制
发表时间：
2019
影响因子：
7.4
通讯作者：
Kreeger,PamelaK
中科院分区：
文献类型：
--
作者：
Kim,ChloeS;Yang,Xinhai;Jacobsen,Sarah;Masters,KristynS;Kreeger,PamelaK
再上皮化是伤口愈合的关键步骤，是角质形成细胞集体迁移的结果。先前的研究表明，固定化但不可溶的表皮生长因子（EGF）导致HaCaT角质形成细胞中磷脂酶Cγ1 （PLCγ1）的领导细胞特异性激活，并且这种PLCγ1的激活对于驱动持续的细胞迁移是必要的。为了确定伤口边缘本地化的plc - γ - 1激活的机制，我们研究了伤口边缘和用载体、可溶性EGF或固定化EGF处理的大块细胞在细胞面积、细胞间相互作用和EGF受体（EGFR）定位方面的差异。我们的研究结果支持一个多步骤机制，其中EGFR从外侧膜转移到基底膜/基底膜允许聚集响应固定的EGF。这种对plc - γ - 1活化调节因子的分析是开发能够调节该信号并因此调节细胞迁移的疗法或伤口敷料的关键一步。
Re‐epithelialization is a critical step in wound healing and results from the collective migration of keratinocytes. Previous work demonstrated that immobilized, but not soluble, epidermal growth factor (EGF) resulted in leader cell‐specific activation of phospholipase C gamma 1 (PLCγ1) in HaCaT keratinocytes, and that this PLCγ1 activation was necessary to drive persistent cell migration. To determine the mechanism responsible for wound edge‐localized PLCγ1 activation, we examined differences in cell area, cell–cell interactions, and EGF receptor (EGFR) localization between wound edge and bulk cells treated with vehicle, soluble EGF, or immobilized EGF. Our results support a multistep mechanism where EGFR translocation from the lateral membrane to the basolateral/basal membrane allows clustering in response to immobilized EGF. This analysis of factors regulating PLCγ1 activation is a crucial step toward developing therapies or wound dressings capable of modulating this signal and, consequently, cell migration.