Chemical and Genetic Tools to Explore SIP Biology

摘要

Abstract The zwitterionic lysophospholipid Sphingosine 1-Phosphate (SIP) is a pleiotropic mediator of physiology and pathology. The synthesis, transport, and degradation of SIP are tightly regulated to ensure that SIP is present in the proper concentrations in the proper location. The binding of SIP to five G protein-coupled SIP receptors regulates many physiological systems, particularly the immune and vascular systems. Our understanding of the functions of SIP has been aided by the tractability of the system to both chemical and genetic manipulation. Chemical modulators have been generated to affect most of the known components of SIP biology, including agonists of SIP receptors and inhibitors of enzymes regulating SIP production and degradation. Genetic knockouts and manipulations have been similarly engineered to disrupt the functions of individual SIP receptors or enzymes involved in SIP metabolism. This chapter will focus on the development and utilization of these chemical and genetic tools to explore the complex biology surrounding SIP and its receptors, with particular attention paid to the in vivo findings that these tools have allowed for.