The sphingosine 1-phosphate receptor-1 (S1PR1) signals in heterogenous populations of mouse adventitial lymphatic (LEC) and arterial endothelial cells (aEC1, aEC2) to regulate chromatin and the transcriptome, thus affecting their phenotypes.
Shortage of blood-borne apolipoprotein-M–bound sphingosine-1-phosphate, which accompanies various brain disorders, causes paracellular leak and increase in transcytosis at the blood–brain barrier, which can be reversed, thus is of clinical relevance.
Constitutive sphingosine 1-phosphate signaling via the G-protein coupled receptor S1PR3 in mechanonociceptive somatosensory neurons is required for normal behavioral responses to noxious mechanical stimuli.
Impairment of the autocrine S1PR1-Gi signaling on HEVs results in high-endothelial cell apoptosis, reduced CCL21-secretion from HEVs, and cessation of HEV-DC interactions and lymphocyte immigration across the high-endothelial barrier.
Developing oocytes lacking Sphk2 sense high sphingosine levels and transcriptionally activate expression of the gene encoding Cers2b, to mediate a salvage pathway to reduce potentially toxic sphingosine.
Disrupting extrusion, a process that drives epithelial cell death, leads to increased cell survival, poor barrier function, and enhanced cell invasion and, thereby, promotes tumor initiation and progression.