Epidermal growth factor receptor kinase activity is required for gap junction closure and for part of the decrease in ovarian follicle cGMP in response to LH.
The meiotic cell cycle in mouse oocytes is arrested in prophase, and then restarted when LH acts on the surrounding granulosa cells. The granulosa cells keep meiosis arrested by providing a source of cGMP that diffuses into the oocyte through gap junctions, and LH restarts the cell cycle by closing the junctions and by decreasing granulosa cell cGMP, thus lowering oocyte cGMP. Epidermal growth factor receptor (EGFR) activation is an essential step in triggering LH-induced meiotic resumption, but its relationship to the cGMP decrease in the follicle is incompletely understood, and its possible function in causing gap junction closure has not been investigated. Here, we use EGFR agonists (epiregulin and amphiregulin) and an EGFR kinase inhibitor (AG1478) to study the function of the EGFR in the signaling pathways leading to the release of oocytes from prophase arrest. Our results indicate that the EGFR kinase contributes to LH-induced meiotic resumption in two different ways. First, it is required for gap junction closure. Second, it is required for an essential component of the decrease in follicle cGMP. Our data show that the EGFR kinase-dependent component of the cGMP decrease is required for LH-induced meiotic resumption, but they also indicate that an as yet unidentified pathway accounts for a large part of the cGMP decrease.
Norris
Rachael P
RP
Department of Cell Biology, University of Connecticut Health Center, Farmington, Connecticut 06032, USA.
Freudzon
Marina
M
Nikolaev
Viacheslav O
VO
Jaffe
Laurinda A
LA
D066258:Amphiregulin; D000818:Animals; D006152:Cyclic GMP / Q000502:physiology*; D066255:EGF Family of Proteins; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066260:Epiregulin; D066246:ErbB Receptors / Q000502:physiology*; D005260:Female; D017629:Gap Junctions / Q000502:physiology*; D006023:Glycoproteins / Q000494:pharmacology; D015151:Immunoblotting; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000502:physiology*; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D006080:Ovarian Follicle / Q000502:physiology*; D011799:Quinazolines; D020032:Tyrphostins / Q000494:pharmacology
D066258:Amphiregulin; C587849:Areg protein, mouse; D066255:EGF Family of Proteins; D066260:Epiregulin; C587881:Ereg protein, mouse; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D011799:Quinazolines; D020032:Tyrphostins; C101044:RTKI cpd; D004815:Epidermal Growth Factor; D007986:Luteinizing Hormone; D066246:ErbB Receptors; D006152:Cyclic GMP
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