Document Detail


Phosphorylation of serine residues in the C-terminal cytoplasmic tail of connexin43 regulates proliferation of ovarian granulosa cells.
MedLine Citation:
PMID:  22729691     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Connexin43 (Cx43) forms gap junctions that couple the granulosa cells of ovarian follicles. In Cx43 knockout mice, follicle growth is restricted as a result of impaired granulosa cell proliferation. We have used these mice to examine the importance of specific Cx43 phosphorylation sites in follicle growth. Serines at residues 255, 262, 279, and 282 are MAP kinase substrates that, when phosphorylated, reduce junctional conductance. Mutant forms of Cx43 were constructed with these serines replaced with amino acids that cannot be phosphorylated. These mutants were transduced into Cx43 knockout ovarian somatic cells that were combined with wild-type oocytes and grafted into immunocompromised female mice permitting follicle growth in vivo. Despite residues 255 or 262 being mutated to prevent their being phosphorylated, recombinant ovaries constructed with these mutants were able to rescue the null phenotype, restoring complete folliculogenesis. In contrast, Cx43 with serine to alanine mutations at both residues 279 and 282 or at all four residues failed to rescue folliculogenesis; the mutant molecules were largely confined to intracellular sites, with few gap junctions. Using an in vitro proliferation assay, we confirmed a decrease in proliferation of granulosa cells expressing the double mutant construct. These results indicate that Cx43 phosphorylation by MAP kinase at serines 279 and 282 occurs in granulosa cells of early follicles and that this is involved in regulating follicle development.
Authors:
Paul W Dyce; Rachael P Norris; Paul D Lampe; Gerald M Kidder
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-06-24
Journal Detail:
Title:  The Journal of membrane biology     Volume:  245     ISSN:  1432-1424     ISO Abbreviation:  J. Membr. Biol.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-07-23     Completed Date:  2012-12-14     Revised Date:  2013-08-30    
Medline Journal Info:
Nlm Unique ID:  0211301     Medline TA:  J Membr Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  291-301     Citation Subset:  IM    
Affiliation:
Department of Physiology and Pharmacology, The University of Western Ontario and Children's Health Research Institute, London, ON N6C 2V5, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Proliferation
Connexin 43 / metabolism*
Female
Granulosa Cells / cytology*,  metabolism*
Mice
Mitogen-Activated Protein Kinases / metabolism
Ovarian Follicle / cytology*,  metabolism*
Ovary / cytology*,  growth & development,  metabolism*
Phosphorylation
Serine / metabolism*
Grant Support
ID/Acronym/Agency:
GM55632/GM/NIGMS NIH HHS; P30 CA015704/CA/NCI NIH HHS; R01 GM055632/GM/NIGMS NIH HHS; //Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/Connexin 43; 56-45-1/Serine; EC 2.7.11.24/Mitogen-Activated Protein Kinases
Comments/Corrections

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