State-dependent signaling by Cav1.2 regulates hair follicle stem cell function

• Published in: Genes & development Vol. 27; no. 11; pp. 1217 - 1222
• Main Authors: Yucel, Gozde, Altindag, Banu, Gomez-Ospina, Natalia, Rana, Anshul, Panagiotakos, Georgia, Lara, Maria Fernanda, Dolmetsch, Ricardo, Oro, Anthony E
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 01.06.2013
• Subjects: Animals; Autistic Disorder; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Calcium Channels, L-Type - genetics; Calcium Channels, L-Type - metabolism; Calcium Signaling - drug effects; Follistatin-Related Proteins - biosynthesis; Follistatin-Related Proteins - metabolism; Hair Follicle - cytology; Long QT Syndrome - metabolism; Mice; Research Communication; Stem Cells - cytology; Stem Cells - drug effects; Stem Cells - metabolism; Syndactyly - metabolism; calcium channel; hair follicle stem cells; VGCC; bulge
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.216556.113

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.