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Control of the T Cell Cortex by the Septin Cytoskeleton


Coordination of immunity requires rapid trafficking of T cells among diverse tissues throughout the body. In their travels, cells can adopt versatile shapes and modes of motility. In lymph nodes and interstitial spaces, T cells crawl rapidly, with an amoeboid morphology characterized by leading edge protrusion and MyoII-based contraction at the trailing uropod. In this work, I have investigated the role of septin GTPases in T cell motility, and in other aspects of T cell biology. Knockdown of septins in D10 T cells results in an uncontrolled cortex with unusual and dynamic blebs and protrusion that lead to inefficient crawling in 2D. Using an osmotic stress model of cortical expansion and contraction, I determined that septins function in the contraction phase of cortical control, assembling at the plasma membrane at stretched, actin-poor regions. My data indicate that septins coordinate the cortex via recapture and contortion of plasma membrane. These findings suggest potentially important roles for septins in migration in vivo, and I have validated a conditional Sept7 knockout mouse model for use in future studies.

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