Asymmetric PI3K Activity in Lymphocytes Organized by a PI3K-Mediated Polarity Pathway
| Autor: | Yen-Hua Chen, Nyanza J. Rothman, Bonnie Yen, Wen-Hsuan W. Lin, Radomir Kratchmarov, William C. Adams, Simone A. Nish, Steven L. Reiner, Jeffrey C. Rathmell |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cell division FOXO1 Cell compartmentation Microbiology Article General Biochemistry Genetics and Molecular Biology Phosphatidylinositol 3-Kinases 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Gene expression Humans Lymphocytes Phosphatidylinositol TCF1 lcsh:QH301-705.5 PI3K/AKT/mTOR pathway Actin Pax5 anabolism Glucose transporter Cell Differentiation asymmetric division Spindle apparatus Cell biology stem cell 030104 developmental biology chemistry lcsh:Biology (General) FoxO1 FOS: Biological sciences mTOR Warburg effect Cytology actin Signal Transduction 030215 immunology |
| Zdroj: | Cell Reports, Vol 22, Iss 4, Pp 860-868 (2018) Cell reports |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY 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 (PIP3) 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. In Brief Activated lymphocytes self-renew while producing differentiated progeny, a process linked to unequal transmission of anabolic PI3K signaling during cell division. Chen et al. find that a PI3K-mediated polarity pathway causes the lopsided arrangement of the very receptors and transporters that mediate PI3K-induced cell fate changes. |
| Databáze: | OpenAIRE |
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