Bovine sperm acrosome reaction induced by G-protein-coupled receptor agonists is mediated by epidermal growth factor receptor transactivation.
We have previously demonstrated the presence of active epidermal growth factor receptor (EGFR) and its involvement in sperm capacitation and the acrosome reaction; however, the mechanism of EGFR activation was not clear. We show here that the sperm EGFR can be transactivated by angiotensin II or by lysophosphatydic acid, two ligands which activate specific G-protein-coupled receptors (GPCR), or by directly activating protein kinase A using 8Br-cAMP. This transactivation occurs in noncapacitated sperm and is mediated by PKA, SRC and a metalloproteinase. We also show that the EGFR is activated in sperm incubated under in vitro capacitation conditions, without any added ligand, but not in bicarbonate-deficient medium or when PKA is blocked. Despite the fact that EGFR is activated in capacitated sperm, this state is not sufficient to induce the acrosome reaction. We conclude that the EGFR is stimulated during capacitation via PKA activation, while further activation of the EGFR in capacitated sperm is required in order to induce the acrosome reaction. The acrosome reaction can be induced by GPCR via the transactivation of the EGFR by a signaling pathway involving PKA, SRC and metalloproteinase and the EGFR down-stream effectors PI3K, PLC and PKC.
Etkovitz
Nir
N
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.
Tirosh
Yitshak
Y
Chazan
Reut
R
Jaldety
Yael
Y
Daniel
Limor
L
Rubinstein
Sara
S
Breitbart
Haim
H
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D020101:Acrosome Reaction / Q000187:drug effects* / Q000502:physiology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D066246:ErbB Receptors / Q000502:physiology*; D008246:Lysophospholipids / Q000494:pharmacology; D008297:Male; D045726:Metalloproteases / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology; D011499:Protein Processing, Post-Translational; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013075:Sperm Capacitation / Q000502:physiology; D015533:Transcriptional Activation; D010738:Type C Phospholipases / Q000502:physiology; D019061:src-Family Kinases / Q000502:physiology
D008246:Lysophospholipids; D043562:Receptors, G-Protein-Coupled; D000804:Angiotensin II; D015124:8-Bromo Cyclic Adenosine Monophosphate; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D019061:src-Family Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D010738:Type C Phospholipases; D045726:Metalloproteases; C032881:lysophosphatidic acid; D002118:Calcium