Bovine sperm acrosome reaction induced by G protein-coupled receptor agonists is mediated by epidermal growth factor receptor transactivation

Nir Etkovitz, Yitshak Tirosh, Reut Chazan, Yael Jaldety, Limor Daniel, Sara Rubinstein, Haim Breitbart

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)447-457
Number of pages11
JournalDevelopmental Biology
Volume334
Issue number2
DOIs
StatePublished - 15 Oct 2009

Bibliographical note

Funding Information:
This research was funded by the Ihel Foundation to HB.

Funding

This research was funded by the Ihel Foundation to HB.

FundersFunder number
Ihel Foundation

    Keywords

    • Acrosome reaction
    • Calcium
    • Kinases
    • Signal transduction
    • Sperm capacitation

    Fingerprint

    Dive into the research topics of 'Bovine sperm acrosome reaction induced by G protein-coupled receptor agonists is mediated by epidermal growth factor receptor transactivation'. Together they form a unique fingerprint.

    Cite this