Zhu Kan, Sun Yaohui, Miu Anh, Yen Michael, Liu Bowei, Zeng Qunli, Mogilner Alex, Zhao Min
Departments of Dermatology and Ophthalmology, Institute for Regenerative Cures, University of California Davis School of Medicine, Sacramento, California.
Bioelectromagnetics Laboratory, Zhejiang University School of Medicine, Hangzhou, China.
J Cell Physiol. 2016 Jun;231(6):1291-300. doi: 10.1002/jcp.25229. Epub 2015 Nov 24.
Cell fragments devoid of the nucleus and major organelles are found in physiology and pathology, for example platelets derived from megakaryocytes, and cell fragments from white blood cells and glioma cells. Platelets exhibit active chemotaxis. Fragments from white blood cells display chemotaxis, phagocytosis, and bactericidal functions. Signaling mechanisms underlying migration of cell fragments are poorly understood. Here we used fish keratocyte fragments and demonstrated striking differences in signal transduction in migration of cell fragments and parental cells in a weak electric field. cAMP or cGMP agonists completely abolished directional migration of fragments, but had no effect on parental cells. The inhibition effects were prevented by pre-incubating with cAMP and cGMP antagonists. Blocking cAMP and cGMP downstream signaling by inhibition of PKA and PKG also recovered fragment galvanotaxis. Both perturbations confirmed that the inhibitory effect was mediated by cAMP or cGMP signaling. Inhibition of cathode signaling with PI3K inhibitor LY294002 also prevented the effects of cAMP or cGMP agonists. Our results suggest that cAMP and cGMP are essential for galvanotaxis of cell fragments, in contrast to the signaling mechanisms in parental cells.
在生理学和病理学中可发现缺乏细胞核和主要细胞器的细胞碎片，例如源自巨核细胞的血小板，以及来自白细胞和胶质瘤细胞的细胞碎片。血小板表现出活跃的趋化性。白细胞碎片具有趋化性、吞噬作用和杀菌功能。细胞碎片迁移的信号传导机制尚不清楚。在这里，我们使用鱼类角膜细胞碎片，并证明在弱电场中细胞碎片和亲代细胞迁移的信号转导存在显著差异。cAMP或cGMP激动剂完全消除了碎片的定向迁移，但对亲代细胞没有影响。通过与cAMP和cGMP拮抗剂预孵育可防止这种抑制作用。通过抑制PKA和PKG来阻断cAMP和cGMP下游信号传导也可恢复碎片的电趋性。这两种干扰均证实抑制作用是由cAMP或cGMP信号传导介导的。用PI3K抑制剂LY294002抑制阴极信号传导也可防止cAMP或cGMP激动剂的作用。我们的结果表明，与亲代细胞的信号传导机制不同，cAMP和cGMP对于细胞碎片的电趋性至关重要。
