EXOCYTOSIS IS TRIGGERED BY SPHINGOSINE 1-PHOSPHATE THROUGH THE ACTIVATION OF S1P RECEPTORS TYPE 1 AND 3

SUHAIMAN, LAILA; DE BLAS, GERARDO A; OBEID, LINA M; DARSZON, ALBERTO; MAYORGA, LUIS S; BELMONTE, SILVIA A

Córdoba

Simposio; First South American Spring Symposium in Signal Transduction and Molecular Medicine (SISTAM 2010; 2010

SISTAM

EXOCYTOSIS IS TRIGGERED BY SPHINGOSINE 1-PHOSPHATE THROUGH THE ACTIVATION OF S1P RECEPTORS TYPE 1 AND 3Laila Suhaiman1, Gerardo A. De Blas1, Lina M. Obeid3, Alberto Darszon2, Luis S. Mayorga1, and Silvia A. Belmonte1Laboratorio de Biología Celular y Molecular, Instituto de Histología y Embriología (IHEM-CONICET), Facultad de Ciencias Médicas, CC56, Universidad Nacional de Cuyo, 5500, Mendoza, Argentina1; Department of Medicine and Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425, USA2 y el Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Morelos, México3Regulated secretion is a central issue for the function of cells; for instance, mammalian sperm acrosomal exocytosis (AE) is essential for egg fertilization. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that regulates crucial physiological processes. S1P triggers AE in human sperm by a mechanism involving a Gi-coupled receptor, PLC and PKC activity. Real-time imaging showed an increase of cytosolic Ca2+ upon activation with S1P and pharmacological experiments indicate that the process requires extracellular Ca2+ influx and efflux from intracellular stores. Sphingosine kinase 1, the enzyme that catalyzes S1P synthesis, is not only present in human sperm but active and required for phorbol ester induced AE. Western blot and immunofluorescence demonstrated that S1P receptors 1 and 3 are present in human sperm cells. Specific agonists and antagonists of these receptors affected the AE suggesting that they are involved in this process. We present here the first piece of evidence indicating that S1P receptors are present in human spermatozoa and involved in the signal transduction cascade triggered by S1P leading to the acrosomal exocytosis