title: The canonical WNT2 pathway and FSH interact to regulate gap junction assembly in mouse granulosa cells.
abstract: WNTs are extracellular signaling molecules that exert their actions through receptors of the frizzled (FZD) family. Previous work indicated that WNT2 regulates cell proliferation in mouse granulosa cells acting through CTNNB1 (beta-catenin), a key component in canonical WNT signaling. In other cells, WNT signaling has been shown to regulate expression of connexin43 (CX43), a gap junction protein, as well as gap junction assembly. Since previous work demonstrated that CX43 is also essential in ovarian follicle development, the objective of this study was to determine if WNT2 regulates CX43 expression and/or gap-junctional intercellular communication (GJIC) in granulosa cells. WNT2 knockdown via siRNA markedly reduced CX43 expression and GJIC. CX43 expression, the extent of CX43-containing gap junction membrane, and GJIC were also reduced by CTNNB1 transient knockdown. CTNNB1 is mainly localized to the membranes between granulosa cells but disappeared from this location after WNT2 knockdown. Furthermore, CTNNB1 knockdown interfered with the ability of follicle-stimulating hormone (FSH) to promote the mobilization of CX43 into gap junctions. We propose that the WNT2/CTNNB1 pathway regulates CX43 expression and GJIC in granulosa cells by modulating CTNNB1 stability and localization in adherens junctions, and that this is essential for FSH stimulation of GJIC.
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada.
authors.forename: Hong-Xing
authors.initials: HX
authors.lastname: Wang
authors.forename: Carolina
authors.initials: C
authors.lastname: Gillio-Meina
authors.forename: Shuli
authors.initials: S
authors.lastname: Chen
authors.forename: Xiang-Qun
authors.initials: XQ
authors.lastname: Gong
authors.forename: Tony Y
authors.initials: TY
authors.lastname: Li
authors.forename: Donglin
authors.initials: D
authors.lastname: Bai
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Kidder
mesh_terms: D022005:Adherens Junctions / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018031:Connexin 43 / Q000378:metabolism*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism* / Q000494:pharmacology; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism*; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D016196:S Phase / Q000187:drug effects / Q000502:physiology; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000502:physiology*; D051154:Wnt2 Protein / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D018031:Connexin 43; D051154:Wnt2 Protein; D051176:beta Catenin; D005640:Follicle Stimulating Hormone
keywords: adherens junction; beta-catenin; connexin43; gap junction; ovarian folliculogenesis