Abstract:
Natural killer (NK) cells patrol tissue to mediate lysis of virally infected and tumorigenic cells. Human NK cells are typically identified by their expression of neural cell adhesion molecule (NCAM, CD56), yet despite its ubiquitous expression on NK cells, CD56 remains a poorly understood protein on immune cells. CD56 has been previously demonstrated to play roles in NK cell cytotoxic function and cell migration. Specifically, CD56-deficient NK cells have impaired cell migration on stromal cells and CD56 is localized to the uropod of NK cells migrating on stroma. Here, we show that CD56 is required for NK cell migration on ICAM-1 and is required for the establishment of persistent cell polarity and unidirectional actin flow. The intracellular domain of CD56 (NCAM-140) is required for its function and the loss of CD56 leads to enlarged actin foci and sequestration of phosphorylated Pyk2 accompanied by increased size and frequency of activated LFA-1 clusters. Together, these data identify a role for CD56 in regulating human NK cell migration through modulation of actin dynamics and integrin turnover.
摘要:
自然杀伤(NK)细胞巡逻组织以介导病毒感染和致瘤细胞的裂解。人类NK细胞通常通过它们表达的神经细胞粘附分子(NCAM,CD56),然而,尽管它在NK细胞上普遍存在,CD56仍然是免疫细胞上鲜为人知的蛋白质。CD56先前已被证明在NK细胞的细胞毒性功能和细胞迁移中起作用。具体来说,CD56缺陷型NK细胞在基质细胞上的细胞迁移受损,CD56定位于在基质上迁移的NK细胞的尾足。这里,我们表明,CD56是NK细胞在ICAM-1上迁移所必需的,并且是建立持续细胞极性和单向肌动蛋白流所必需的。CD56(NCAM-140)的胞内结构域是其功能所必需的,而CD56的丢失导致肌动蛋白灶扩大和磷酸化Pyk2的螯合,并伴随着激活的LFA-1簇的大小和频率增加。一起,这些数据确定了CD56通过调节肌动蛋白动力学和整合素转换在调节人类NK细胞迁移中的作用。[媒体:见文本][媒体:见文本][媒体:见文本][媒体:见文本][媒体:见文本][媒体:见文本][媒体:见文本][媒体:见文本]。