Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Vanderbilt Center for Immunobiology, Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Cell Rep. 2018 Jan 23;22(4):860-868. doi: 10.1016/j.celrep.2017.12.087. Epub 2018 Jan 28.
Unequal transmission of nutritive signaling during cell division establishes fate disparity between sibling lymphocytes, but how asymmetric signaling becomes organized is not understood. We show that receptor-associated class I phosphatidylinositol 3-kinase (PI3K) signaling activity, indexed by phosphatidylinositol (3,4,5)-trisphosphate (PIP) staining, is spatially restricted to the microtubule-organizing center and subsequently to one pole of the mitotic spindle in activated T and B lymphocytes. Asymmetric PI3K activity co-localizes with polarization of antigen receptor components implicated in class I PI3K signaling and with facultative glucose transporters whose trafficking is PI3K dependent and whose abundance marks cells destined for differentiation. Perturbation of class I PI3K activity disrupts asymmetry of upstream antigen receptors and downstream glucose transporter traffic. The roles of PI3K signaling in nutrient utilization, proliferation, and gene expression may have converged with the conserved role of PI3K signaling in cellular symmetry breaking to form a logic for regenerative lymphocyte divisions.
细胞分裂过程中营养信号的不均等传递在兄弟姐妹淋巴细胞之间建立了命运差异，但不对称信号如何组织尚不清楚。我们表明，受体相关的 class I 磷脂酰肌醇 3-激酶 (PI3K) 信号活性，由磷脂酰肌醇 (3,4,5)-三磷酸 (PIP) 染色标记，在激活的 T 和 B 淋巴细胞中空间上局限于微管组织中心，随后局限于有丝分裂纺锤体的一极。不对称的 PI3K 活性与涉及 class I PI3K 信号的抗原受体成分的极化以及与易位的葡萄糖转运蛋白共定位，后者的易位依赖于 PI3K，其丰度标志着细胞注定要分化。干扰 class I PI3K 活性会破坏上游抗原受体和下游葡萄糖转运蛋白运输的不对称性。PI3K 信号在营养利用、增殖和基因表达中的作用可能与 PI3K 信号在细胞对称性破坏中的保守作用相融合，形成了再生性淋巴细胞分裂的逻辑。
