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S1P Receptor

In vertebrates, S1P is found in the extracellular milieu and interacts with cell-surface receptors to regulate an array of cellular responses, including cell migration, differentiation and survival. S1P plays fundamental roles in morphogenetic mechanisms, such as collective cell migration, tissue inductive events and biomechanical signalling. S1P receptors exhibit unique as well as common G-proteincoupling properties. For example, S1P1 couples exclusively to the Gi/o family, whereas S1P2 is capable of coupling to Gi/o, to G12/13 as well as to the Gq family. This coupling results in the activation of small GTPases such as Rho, Rac and Ras. Further downstream effectors of S1P receptors include adenylate cylase, PI-3-kinase, phospholipase C, protein kinase C and intracellular calcium. S1P2 receptor activation results in Rho, Rho kinase and PTEN signalling, which disrupts adherens junctions. This receptor also inhibits cell migration induced by growth factors, such as platelet-derived growth factor (PDGF) and insulin-like growth factor (IGF), and chemokines, such as stromal-derived factor 1 (SDF1, CXCL12), C5a and CCL2. S1P signalling affects the collective behaviour of cells by regulating cell-matrix and cell-cell adhesion, as well as alterations to the cytoskeleton. As this signalling system is involved in human diseases, and given that therapeutic modulation of S1P receptors has just begun in the treatment of neuroinflammatory diseases, developmental insights may be useful in further application to human therapeutics.

References

1.Mendelson K,et al. Development. 2014;141(1):5–9.

GPCR/G Protein

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