Journal article
Luteinizing Hormone Receptor-Stimulated Progesterone Production by Preovulatory Granulosa Cells Requires Protein Kinase A-Dependent Activation/Dephosphorylation of the Actin Dynamizing Protein Cofilin
Molecular endocrinology (Baltimore, Md.), Vol.24(9), pp.1765-1781
09/01/2010
Handle:
https://hdl.handle.net/2376/110517
PMCID: PMC2940477
PMID: 20610540
Abstract
Abstract
Activation of the LH receptor (LHR) on preovulatory granulosa cells stimulates the cAMP/protein kinase A (PKA) pathway to regulate expression of genes required for ovulation and luteinization. LHR signaling also initiates rearrangement of the actin cytoskeleton. Because disruption of the actin cytoskeleton has been causally linked to steroidogenesis in various cell models, we sought to identify the cellular mechanisms that may modulate reorganization of the actin cytoskeleton and to determine whether cytoskeletal reorganization is required for steroidogenesis. Herein we report that LHR signaling in preovulatory granulosa cells promotes rapid dephosphorylation of the actin-depolymerizing factor cofilin at Ser3 that is dependent on PKA. The LHR-stimulated dephosphorylation of cofilin(Ser3) switches on cofilin activity to bind actin filaments and enhance their dynamics. Basal phosphorylation of cofilin(Ser3) is mediated by active/GTP-bound Rho and downstream protein kinases; LHR signaling promotes a decrease in active/GTP-bound Rho by a PKA-dependent mechanism. LHR-dependent Rho inactivation and subsequent activation of cofilin does not involve ERK, epidermal growth factor receptor, or phosphatidylinositol 3-kinase pathways downstream of PKA. To understand the biological significance of cofilin activation, preovulatory granulosa cells were transduced with a mutant cofilin adenoviral vector in which Ser3 was mutated to Glu (S-E cofilin). Inactive S-E cofilin abolished LHR-mediated reorganization of the actin cytoskeleton and caused a 70% decrease in LHR-stimulated progesterone that is obligatory for ovulation. Taken together, these results show that LHR signaling via PKA activates a cofilin-regulated rearrangement of the actin cytoskeleton and that active cofilin is required to initiate progesterone secretion by preovulatory granulosa cells.
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- Title
- Luteinizing Hormone Receptor-Stimulated Progesterone Production by Preovulatory Granulosa Cells Requires Protein Kinase A-Dependent Activation/Dephosphorylation of the Actin Dynamizing Protein Cofilin
- Creators
- Amelia B Karlsson - 1Department of Cell and Molecular Biology (A.B.K., E.T.M., M.P.F, J.C.J., M.H.-D.), Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611Evelyn T Maizels - 1Department of Cell and Molecular Biology (A.B.K., E.T.M., M.P.F, J.C.J., M.H.-D.), Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611Maxfield P Flynn - 1Department of Cell and Molecular Biology (A.B.K., E.T.M., M.P.F, J.C.J., M.H.-D.), Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611Jonathan C Jones - 1Department of Cell and Molecular Biology (A.B.K., E.T.M., M.P.F, J.C.J., M.H.-D.), Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611Eric A Shelden - 2School of Molecular Biosciences (A.B.K., M.H.-D., E.A.S.), Washington State University, Pullman, Washington 99164James R Bamburg - 3Department of Biochemistry and Molecular Biology (J.R.B.), Colorado State University, Fort Collins, Colorado 80523Mary Hunzicker-Dunn - 1Department of Cell and Molecular Biology (A.B.K., E.T.M., M.P.F, J.C.J., M.H.-D.), Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611
- Publication Details
- Molecular endocrinology (Baltimore, Md.), Vol.24(9), pp.1765-1781
- Academic Unit
- Molecular Biosciences, School of
- Publisher
- Oxford University Press
- Identifiers
- 99900547047801842
- Language
- English
- Resource Type
- Journal article