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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.

SUBMITTER: Yucel G

PROVIDER: S-EPMC3690395 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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

Yucel Gozde G Altindag Banu B Gomez-Ospina Natalia N Rana Anshul A Panagiotakos Georgia G Lara Maria Fernanda MF Dolmetsch Ricardo R Oro Anthony E AE

Genes & development 20130601 11

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 p ...[more]

PMID: 23752588

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