dc.contributor.author |
Suhaiman, L |
|
dc.contributor.author |
De Blas, GA |
|
dc.contributor.author |
Obeid, LM |
|
dc.contributor.author |
Darszon, A |
|
dc.contributor.author |
Mayorga, LS |
|
dc.contributor.author |
Belmonte, SA |
|
dc.date.accessioned |
2011-01-21T10:35:24Z |
|
dc.date.available |
2011-01-21T10:35:24Z |
|
dc.date.issued |
2010 |
|
dc.identifier.issn |
0021-9258 |
|
dc.identifier.uri |
http://hdlhandlenet/123456789/218 |
|
dc.description.abstract |
Regulated secretion is a central issue for the specific function of many cells |
en_US |
dc.description.abstract |
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 G(i)-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 calcium influx through voltage and store-operated calcium channels and efflux from intracellular stores through inositol 1,4,5-trisphosphate-sensitive calcium channels. Sphingosine 1-phosphate-induced exocytosis requires phospholipase C 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 showed that phorbol ester-induced exocytosis depends on the activation of sphingosine kinase 1. Furthermore, incorporation of P-32 to sphingosine demonstrates that cells treated with the phorbol ester increase their sphingosine kinase activity that yields sphingosine 1-phosphate. We present here the first evidence indicating that human spermatozoa produce sphingosine 1-phosphate 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. |
en_US |
dc.language.iso |
en |
en_US |
dc.title |
Sphingosine 1-Phosphate and Sphingosine Kinase Are Involved in a Novel Signaling Pathway Leading to Acrosomal Exocytosis |
en_US |
dc.type |
Article |
en_US |
dc.identifier.idprometeo |
64 |
|
dc.identifier.doi |
10.1074/jbc.M109.072439 |
|
dc.source.novolpages |
285(21):16302-16314 |
|
dc.subject.wos |
Biochemistry & Molecular Biology |
|
dc.description.index |
WoS: SCI, SSCI o AHCI |
|
dc.relation.journal |
Journal of Biological Chemistry |
|