Abstract
By hydrolyzing its substrate sphingomyelin at the cytosolic leaflet of cellular membranes, the neutral sphingomyelinase 2 (NSM2) generates microdomains which serve as docking sites for signaling proteins and thereby, functions to regulate signal relay. This has been particularly studied in cellular stress responses while the regulatory role of this enzyme in the immune cell compartment has only recently emerged. In T cells, phenotypic polarization by co-ordinated cytoskeletal remodeling is central to motility and interaction with endothelial or antigen-presenting cells during tissue recruitment or immune synapse formation, respectively. This review highlights studies adressing the role of NSM2 in T cell polarity in which the enzyme plays a major role in regulating cytoskeletal dynamics.
Acknowledgments
We apologize to all our colleagues whose exciting work we were not able to include due to space limits. We thank Erich Gulbins, Jürgen Schneider-Schaulies and Niklas Beyersdorf for helpful discussions in preparing this article. The authors are grateful to the DFG for funding their work (Funder ID: 10.13039/501100001659, Grant no. SCHN405/10-1 and 10-2).
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