title: State-dependent signaling by Cav1.2 regulates hair follicle stem cell function.
abstract: The signals regulating stem cell activation during tissue regeneration remain poorly understood. We investigated the baldness associated with mutations in the voltage-gated calcium channel (VGCC) Cav1.2 underlying Timothy syndrome (TS). While hair follicle stem cells express Cav1.2, they lack detectable voltage-dependent calcium currents. Cav1.2(TS) acts in a dominant-negative manner to markedly delay anagen, while L-type channel blockers act through Cav1.2 to induce anagen and overcome the TS phenotype. Cav1.2 regulates production of the bulge-derived BMP inhibitor follistatin-like1 (Fstl1), derepressing stem cell quiescence. Our findings show how channels act in nonexcitable tissues to regulate stem cells and may lead to novel therapeutics for tissue regeneration.
authors.affiliation: Program in Epithelial Biology, Stanford University, School of Medicine, Stanford, California 94305, USA.
authors.forename: Gozde
authors.initials: G
authors.lastname: Yucel
authors.forename: Banu
authors.initials: B
authors.lastname: Altindag
authors.forename: Natalia
authors.initials: N
authors.lastname: Gomez-Ospina
authors.forename: Anshul
authors.initials: A
authors.lastname: Rana
authors.forename: Georgia
authors.initials: G
authors.lastname: Panagiotakos
authors.forename: Maria Fernanda
authors.initials: MF
authors.lastname: Lara
authors.forename: Ricardo
authors.initials: R
authors.lastname: Dolmetsch
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Oro
mesh_terms: D000818:Animals; D001321:Autistic Disorder; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D038702:Follistatin-Related Proteins / Q000096:biosynthesis / Q000378:metabolism; D018859:Hair Follicle / Q000166:cytology*; D008133:Long QT Syndrome / Q000378:metabolism; D051379:Mice; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D013576:Syndactyly / Q000378:metabolism
chemical_list: C514350:CACNA1C protein, mouse; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D038702:Follistatin-Related Proteins; C448720:Fstl1 protein, mouse; D002118:Calcium
keywords: VGCC; bulge; calcium channel; hair follicle stem cells