INVESTIGADORES
MAYORGA Luis Segundo
artículos
Título:
Sphingosine 1-phosphate and sphingosine kinase are involved in a novel signaling pathway leading to acrosomal exocytosis.
Autor/es:
SUHAIMAN, L; DE BLAS, G; OBEID, LM; DARSZON, A.; MAYORGA, L.S.; BELMONTE, SA
Revista:
JOURNAL OF BIOLOGICAL CHEMISTRY
Editorial:
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Referencias:
Año: 2010 vol. 285 p. 16302 - 16314
ISSN:
0021-9258
Resumen:
Regulated secretion is a central issue for thespecific function of many cells; for instance,mammalian sperm acrosomal exocytosis isessential for egg fertilization. Sphingosine 1-phosphate is a bioactive sphingolipid thatregulates crucial physiological processes. Herewe report that this lipid triggers acrosomalexocytosis in human sperm by a mechanisminvolving a Gi-coupled receptor. Real timeimaging showed a remarkable increase ofcytosolic calcium upon activation withsphingosine 1-phosphate and pharmacologicalexperiments indicate that the process requiresextracellular calcium influx through voltageand store operated calcium channels and effluxfrom intracellular stores through inositol 1,4,5-trisphosphate-sensitive calcium channels.Sphingosine 1-phosphate-induced exocytosisrequires phospholipase C and protein kinase Cactivation. We investigated possible sources ofthe lipid. Western blot indicates thatsphingosine kinase 1 is present in spermatozoa.Indirect immunofluorescence showed thatphorbol ester?a potent protein kinase Cactivator that can also trigger acrosomalexocytosis? redistributes sphingosine kinase 1to the acrosomal region. Functional assaysshowed that phorbol ester-induced exocytosisdepends on the activation of sphingosine kinase1. Furthermore, incorporation of 32P tosphingosine demonstrates that cells treatedwith the phorbol ester increase theirsphingosine kinase activity renderingsphingosine 1-phosphate. We present here thefirst evidence indicating that humanspermatozoa produce sphingosine 1-phosphatewhen challenged with an exocytic stimulus.These observations point to a new role ofsphingosine 1-phosphate in a signaling cascadethat facilitates acrosome reaction providingsome clues about