Asymmetric PI3K Activity in Lymphocytes Organized by a PI3K-Mediated Polarity Pathway
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 phos...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-01-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717319241 |
| _version_ | 1811331159073751040 |
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| author | Yen-Hua Chen Radomir Kratchmarov Wen-Hsuan W. Lin Nyanza J. Rothman Bonnie Yen William C. Adams Simone A. Nish Jeffrey C. Rathmell Steven L. Reiner |
| author_facet | Yen-Hua Chen Radomir Kratchmarov Wen-Hsuan W. Lin Nyanza J. Rothman Bonnie Yen William C. Adams Simone A. Nish Jeffrey C. Rathmell Steven L. Reiner |
| author_sort | Yen-Hua Chen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T16:15:48Z |
| format | Article |
| id | doaj.art-7461fd78f1ed4b0c926b4242d57a9d12 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-13T16:15:48Z |
| publishDate | 2018-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-7461fd78f1ed4b0c926b4242d57a9d122022-12-22T02:40:04ZengElsevierCell Reports2211-12472018-01-0122486086810.1016/j.celrep.2017.12.087Asymmetric PI3K Activity in Lymphocytes Organized by a PI3K-Mediated Polarity PathwayYen-Hua Chen0Radomir Kratchmarov1Wen-Hsuan W. Lin2Nyanza J. Rothman3Bonnie Yen4William C. Adams5Simone A. Nish6Jeffrey C. Rathmell7Steven L. Reiner8Department of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USADepartment of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USADepartment of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USADepartment of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USADepartment of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USADepartment of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USADepartment of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USAVanderbilt Center for Immunobiology, Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USADepartment of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USAUnequal 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.http://www.sciencedirect.com/science/article/pii/S2211124717319241TCF1FoxO1Pax5mTORstem cellanabolismWarburg effectasymmetric divisionactin |
| spellingShingle | Yen-Hua Chen Radomir Kratchmarov Wen-Hsuan W. Lin Nyanza J. Rothman Bonnie Yen William C. Adams Simone A. Nish Jeffrey C. Rathmell Steven L. Reiner Asymmetric PI3K Activity in Lymphocytes Organized by a PI3K-Mediated Polarity Pathway Cell Reports TCF1 FoxO1 Pax5 mTOR stem cell anabolism Warburg effect asymmetric division actin |
| title | Asymmetric PI3K Activity in Lymphocytes Organized by a PI3K-Mediated Polarity Pathway |
| title_full | Asymmetric PI3K Activity in Lymphocytes Organized by a PI3K-Mediated Polarity Pathway |
| title_fullStr | Asymmetric PI3K Activity in Lymphocytes Organized by a PI3K-Mediated Polarity Pathway |
| title_full_unstemmed | Asymmetric PI3K Activity in Lymphocytes Organized by a PI3K-Mediated Polarity Pathway |
| title_short | Asymmetric PI3K Activity in Lymphocytes Organized by a PI3K-Mediated Polarity Pathway |
| title_sort | asymmetric pi3k activity in lymphocytes organized by a pi3k mediated polarity pathway |
| topic | TCF1 FoxO1 Pax5 mTOR stem cell anabolism Warburg effect asymmetric division actin |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717319241 |
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