INVESTIGADORES
SUHAIMAN Laila
congresos y reuniones científicas
Título:
Sphingosine 1-phosphate and sphingosine kinase 1: new players in calcium regulated exocytosis
Autor/es:
SUHAIMAN, LAILA; DE BLAS, GERARDO A; OBEID, LINA M; DARSZON, ALBERTO; MAYORGA, LUIS S; BELMONTE, SILVIA A
Lugar:
Holderness School, Holderness, New Hampshire, USA
Reunión:
Conferencia; Gordon Research Conference: Fertilization and Activation of Development; 2009
Institución organizadora:
Gordon Research Conference
Resumen:
Regulated secretion is a central issue for the specific function of many cells; for instance, mammalian sperm acrosomal exocytosis is essential for egg fertilization. Sphingosine 1-phosphate is a bioactive sphingolipid that regulates crucial physiological processes. Here we report that this lipid triggers acrosomal exocytosis in human sperm by a mechanism involving a Gi-coupled receptor. Real time imaging showed a remarkable increase of cytosolic calcium upon activation with sphingosine 1-phosphate and pharmacological experiments indicate that the process requires extracellular Ca2+ influx through voltage and store operated calcium channels and efflux from intracellular stores through IP3-sensitive Ca2+ channels. Sphingosine 1-phosphate-induced exocytosis requires phospholipase C, protein kinase A, and protein kinase C activation. We investigated possible sources of the lipid. Western blot indicates that sphingosine kinase 1 is present in spermatozoa. Indirect immunofluorescence showed that phorbol ester-a potent protein kinase C activator that can also trigger acrosomal exocytosis redistributes sphingosine kinase 1 to the acrosomal region. Functional assays indicate that phorbol ester-induced exocytosis depends on the activation of sphingosine kinase 1 (SK). Furthermore, incorporation of 32P to sphingosine demonstrates that cells treated with the phorbol ester increase their SK activity rendering sphingosine 1-phosphate. We present here the first evidence indicating that human spermatozoa produces the sphingolipid when challenged with an exocytic stimulus. These observations point to a new role of sphingosine 1-phosphate in a signaling cascade that facilitates acrosome reaction providing some clues about novel lipid molecules involved in exocytosis.