Molecular mechanism for human sperm chemotaxis mediated by progesterone.
Sperm chemotaxis is a chemical guiding mechanism that may orient spermatozoa to the egg surface. A picomolar concentration gradient of Progesterone (P), the main steroidal component secreted by the cumulus cells that surround the egg, attracts human spermatozoa. In order to elucidate the molecular mechanism of sperm chemotaxis mediated by P, we combine the application of different strategies: pharmacological inhibition of signaling molecules, measurements of the concentrations of second messengers and activation of the chemotactic signaling. Our data implicate a number of classic signal transduction pathways in the response and provide a model for the sequence of events, where the tmAC-cAMP-PKA pathway is activated first, followed by protein tyrosine phosphorylation (equatorial band and flagellum) and calcium mobilization (through IP(3)R and SOC channels), whereas the sGC-cGMP-PKG cascade, is activated later. These events lead to sperm orientation towards the source of the chemoattractant. The finding proposes a molecular mechanism which contributes to the understanding of the signal transduction pathway that takes place in a physiological process as chemotaxis.
Teves
Maria E
ME
Centro de Biología Celular y Molecular, Universidad Nacional de Córdoba, Córdoba, Argentina.
Guidobaldi
Hector A
HA
Uñates
Diego R
DR
Sanchez
Raul
R
Miska
Werner
W
Publicover
Stephen J
SJ
Morales Garcia
Aduén A
AA
Giojalas
Laura C
LC
D000262:Adenylyl Cyclases / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D008297:Male; D019000:Phosphotyrosine / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D013094:Spermatozoa / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology
D015220:Calcium Channels; D019000:Phosphotyrosine; D011374:Progesterone; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D002118:Calcium