@phdthesis{Collenburg2018, author = {Collenburg, Lena}, title = {The Role of Ceramides and Sphingomyelinases for Dynamic Membrane Processes in T Cells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151161}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {Previous work of our group has established a role of sphingomyelinases in the regulation of T cell responses to TCR or pathogen stimulation, and this became particularly evident at the level of actin cytoskeletal dynamics. The formation of lipid membrane microdomains is crucial for receptor clustering and signal induction, and therefore, ceramide accumulation by membrane sphingomyelin breakdown is needed for signalling- complex-assembly. Pathogen-induced overshooting of SMase activation substantially impacted the formation of membrane protrusions, with T cell spreading as well as a front/rear polarisation upon CD3/CD28 co-stimulation [103]. On the other hand, NSM activation is part of the physiological TCR signal [67], indicating that a spatiotemporally balanced NSM activation is crucial for its physiological function. It involves actin cytoskeletal reorganisation and T cell polarisation. These two functions are also of central importance in directional T cell migration and motility in tissues. This thesis aims on defining the role of NSM in compartmentalisation of the T cell membrane in polarisation and migration. Therefore, functional studies on the impact of NSM activity in these processes had to be complemented by the development of tools to study ceramide compartmentalisation in living T cells.}, subject = {Ceramides}, language = {en} }