SFB 854/3 B12: ADAPtive T cell migration into the stressed brain

T cell migration ensures the homing of T cells to different peripheral organs and tissues, including the brain. The
Adhesion- and Degranulation-promoting Adaptor Protein (ADAP) and its constitutive interaction partner the Src
Kinase Associated Phosphoprotein of 55 kDa (SKAP55) are critical components of an intracellular signaling
platform that mediates the activation of integrins and actin dynamics during adhesion and migration. In the 2nd
CRC854 funding period we showed that ADAP and SKAP55 both harbor either direct or indirect actin effector
sites. In addition, we identified individual post-translational modifications in ADAP that modulate the F-actin
content and the migratory properties of T cells. During the 3rd funding period we seek to investigate the molecular basis for actin regulation by the ADAP/SKAP55-module during T cell migration. We will use structural,
biochemical and molecular biology techniques to determine the relevant molecular sites and interaction partners of the ADAP/SKAP55-module that control the architecture of the actin cytoskeleton. We will translate our molecular and structural insights into a functional analysis at both the cellular and the organ level. T cells use integrin signaling and actin to migrate into the brain after a stress stimulus and we seek to investigate how the ADAP/SKAP55-module might regulate these processes. In particular, we will investigate the role of the ADAP/SKAP55-module with regard to the recently recognized function of T cells in protecting against the debilitating effects of traumatic stress
exposure.