title: Control of mammary myoepithelial cell contractile function by α3β1 integrin signalling.
abstract: In the functionally differentiated mammary gland, basal myoepithelial cells contract to eject the milk produced by luminal epithelial cells from the body. We report that conditional deletion of a laminin receptor, α3β1 integrin, from myoepithelial cells leads to low rates of milk ejection due to a contractility defect but does not interfere with the integrity or functional differentiation of the mammary epithelium. In lactating mammary gland, in the absence of α3β1, focal adhesion kinase phosphorylation is impaired, the Rho/Rac balance is altered and myosin light-chain (MLC) phosphorylation is sustained. Cultured mammary myoepithelial cells depleted of α3β1 contract in response to oxytocin, but are unable to maintain the state of post-contractile relaxation. The expression of constitutively active Rac or its effector p21-activated kinase (PAK), or treatment with MLC kinase (MLCK) inhibitor, rescues the relaxation capacity of mutant cells, strongly suggesting that α3β1-mediated stimulation of the Rac/PAK pathway is required for the inhibition of MLCK activity, permitting completion of the myoepithelial cell contraction/relaxation cycle and successful lactation. This is the first study highlighting the impact of α3β1 integrin signalling on mammary gland function.
authors.affiliation: Institut Curie, Centre de Recherche, Paris, France. karine.raymond@curie.fr
authors.forename: Karine
authors.initials: K
authors.lastname: Raymond
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Cagnet
authors.forename: Maaike
authors.initials: M
authors.lastname: Kreft
authors.forename: Hans
authors.initials: H
authors.lastname: Janssen
authors.forename: Arnoud
authors.initials: A
authors.lastname: Sonnenberg
authors.forename: Marina A
authors.initials: MA
authors.lastname: Glukhova
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004848:Epithelium / Q000502:physiology*; D017353:Gene Deletion; D039201:Integrin alpha3beta1 / Q000235:genetics / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000166:cytology*; D051379:Mice; D032342:Muscle Cells / Q000502:physiology*; D009119:Muscle Contraction; D009126:Muscle Relaxation
chemical_list: D039201:Integrin alpha3beta1