Laboratory of Developmental Neurobiology, National Heart Lung and Blood Institute, NIH, Bethesda, MD, 20892, USA.
Laboratory of Developmental Neurobiology, National Heart Lung and Blood Institute, NIH, Bethesda, MD, 20892, USA; Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC, USA.
Exp Cell Res. 2020 Apr 15;389(2):111911. doi: 10.1016/j.yexcr.2020.111911. Epub 2020 Feb 14.
Phospholipid Phosphatase-Related Protein Type 1 (PLPPR1) is a six-transmembrane protein that belongs to the family of plasticity-related gene proteins, which is a novel brain-specific subclass of the lipid phosphate phosphatase superfamily. PLPPR1-5 have prominent roles in synapse formation and axonal pathfinding. We found that PLPPR1 overexpression in the mouse neuroblastoma cell line (Neuro2a) results in increase in cell adhesion and reduced cell migration. During migration, these cells leave behind long fibrous looking extensions of the plasma membrane causing a peculiar phenotype. Cells expressing PLPPR1 showed decreased actin turnover and decreased disassembly of focal adhesions. PLPPR1 also reduced active Rac1, and expressing dominant negative Rac1 produced a similar phenotype to overexpression of PLPPR1. The PLPPR1-induced phenotype of long fibers was reversed by introducing constitutively active Rac1. In summary, we show that PLPPR1 decreases active Rac1 levels that leads to cascade of events which increases cell adhesion.
磷酸酶相关蛋白 1 型(PLPPR1)是一种六次跨膜蛋白,属于可塑性相关基因蛋白家族,是脂质磷酸酶超级家族中的一个新型脑特异性亚类。PLPPR1-5 在突触形成和轴突寻径中发挥重要作用。我们发现,在小鼠神经母细胞瘤细胞系(Neuro2a)中过表达 PLPPR1 会导致细胞黏附增加和细胞迁移减少。在迁移过程中,这些细胞在细胞膜上留下长长的纤维状延伸,导致一种特殊的表型。表达 PLPPR1 的细胞表现出肌动蛋白周转率降低和焦点黏附解聚减少。PLPPR1 还减少了活性 Rac1 的表达,表达显性失活 Rac1 会产生类似于过表达 PLPPR1 的表型。通过引入组成性激活的 Rac1,PLPPR1 诱导的长纤维表型得到逆转。总之,我们表明 PLPPR1 降低了活性 Rac1 水平,导致一系列增加细胞黏附的事件。