1. Immature T-cell clustering and efficient differentiation require the polarity protein Scribble.
- Author
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Pike KA, Kulkarni S, and Pawson T
- Subjects
- Animals, Cell Aggregation immunology, Flow Cytometry, Hematopoietic Stem Cells immunology, Intracellular Signaling Peptides and Proteins metabolism, Mice, Microscopy, Confocal, T-Lymphocytes immunology, Cell Differentiation immunology, Cell Polarity immunology, Hematopoietic Stem Cells cytology, Intracellular Signaling Peptides and Proteins immunology, T-Lymphocytes cytology
- Abstract
T-cell polarization is required for cell migration and cell-cell interactions, cellular behaviors crucial for lymphocyte differentiation. Despite expression of the epithelial polarity network in T cells, neither its contribution to thymocyte polarity nor its requirement during development is known. We report here that depletion of the polarity protein Scribble in hematopoietic progenitor cells results in inefficient T-cell development characterized by a partial developmental block during the early double-negative (DN) stage of differentiation. Scribble-depleted hematopoietic progenitor cells exhibit a delayed transition into late CD44(lo/-)CD25(+) DN3 cells, evidenced by the accumulation of early CD44(int)CD25(+) DN3 cells. As a consequence, a limited cellular expansion and a reduced frequency of intracellular T-cell receptor β-positive DN3 cells are observed among Scribble-deficient differentiating T cells. Moreover, whereas purified Scribble-depleted DN2 and DN3 cells do not exhibit compromised spontaneous motility, T-cell clustering and prolonged homotypic interactions among such cells are reduced. This deficiency correlates with a lack of polarization of the integrin LFA-1 during T-cell migration or on the initiation of T-cell-T-cell interactions. Scribble is therefore a critical contributor to the clustering of immature T cells, an event shown here to be necessary for efficient developmental progression.
- Published
- 2011
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