PDF(Pubmed)
Abstract：
Little is known about eukaryotic chemorepulsion. The enzymes phosphatase and tensin homolog (PTEN) and CnrN dephosphorylate phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] to phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. Dictyostelium discoideum cells require both PTEN and CnrN to induce chemorepulsion of cells away from the secreted chemorepellent protein AprA. How D. discoideum cells utilize two proteins with redundant phosphatase activities in response to AprA is unclear. Here, we show that D. discoideum cells require both PTEN and CnrN to locally inhibit Ras activation, decrease basal levels of PI(3,4,5)P3 and increase basal numbers of macropinosomes, and AprA prevents this increase. AprA requires both PTEN and CnrN to increase PI(4,5)P2 levels, decrease PI(3,4,5)P3 levels, inhibit proliferation, decrease myosin II phosphorylation and increase filopod sizes. PTEN, but not CnrN, decreases basal levels of PI(4,5)P2, and AprA requires PTEN, but not CnrN, to induce cell roundness. Together, our results suggest that CnrN and PTEN play unique roles in AprA-induced chemorepulsion.
摘要：
对真核细胞化学排斥知之甚少。磷酸酶和张力蛋白同源物（PTEN）和CnrN酶将磷脂酰肌醇3,4,5-三磷酸[PI（3,4,5）P3]去磷酸化为磷脂酰肌醇4,5-双磷酸[PI（4,5）P2]。盘基网柄菌细胞需要PTEN和CnrN两者来诱导细胞的化学排斥远离分泌的化学反应蛋白AprA。盘状D.discoideum细胞如何利用两种具有冗余磷酸酶活性的蛋白质来响应AprA尚不清楚。这里,我们显示盘状D.discoideum细胞需要PTEN和CnrN来局部抑制Ras激活，降低PI（3,4,5）P3的基础水平，并增加大黄体的基础数量，AprA阻止了这种增加。AprA需要PTEN和CnrN来增加PI（4,5）P2水平，降低PI(3,4,5)P3水平，抑制增殖，减少肌球蛋白II磷酸化，并增加filopod的大小。PTEN,但不是CnrN，降低PI(4,5)P2的基础水平，AprA需要PTEN，但不是CnrN，诱导细胞圆度。一起,我们的结果表明，CnrN和PTEN在AprA诱导的化学排斥中起着独特的作用。
