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Asymmetric PI3K Activity in Lymphocytes Organized by a PI3K-Mediated Polarity Pathway
Yen-Hua Chen1, Radomir Kratchmarov1, Wen-Hsuan W Lin1
1Department 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.
Cell Reports
|February 9, 2018
Summary
Asymmetric phosphatidylinositol 3-kinase (PI3K) signaling organizes cell division in lymphocytes. This asymmetry directs nutrient signaling, influencing cell fate and differentiation for regenerative divisions.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Cell division typically produces equipotent daughter cells.
- Lymphocyte fate disparity arises from unequal transmission of nutritive signals during division.
- The mechanisms organizing asymmetric signaling remain unclear.
Purpose of the Study:
- To investigate the spatial organization of asymmetric signaling during lymphocyte division.
- To elucidate the role of phosphatidylinositol 3-kinase (PI3K) signaling in establishing cell fate disparity.
- To understand how PI3K signaling contributes to regenerative lymphocyte divisions.
Main Methods:
- Utilized phosphatidylinositol (3,4,5)-trisphosphate (PIP3) staining to visualize PI3K activity.
- Observed spatial localization of PI3K activity relative to the mitotic spindle.
- Perturbed PI3K activity to assess its impact on cellular asymmetry and nutrient transporter trafficking.
Main Results:
- Asymmetric PI3K signaling activity was spatially restricted to the microtubule-organizing center and one pole of the mitotic spindle in T and B lymphocytes.
- This asymmetry co-localized with polarized antigen receptor components and glucose transporters.
- Disruption of PI3K activity abolished asymmetry of antigen receptors and glucose transporter traffic.
Conclusions:
- Receptor-associated class I PI3K signaling is crucial for breaking cellular symmetry during lymphocyte division.
- PI3K-dependent asymmetric signaling regulates nutrient transporter trafficking and cell fate.
- Convergent roles of PI3K in nutrient utilization and symmetry breaking establish a logic for regenerative lymphocyte divisions.
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