State-dependent signaling by Cav1.2 regulates hair follicle stem cell function
Open accessAbstract
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) Ca v 1.2 underlying Timothy syndrome (TS). While hair follicle stem cells express Ca v 1.2, they lack detectable voltage-dependent calcium currents. Ca v 1.2 TS acts in a dominant-negative manner to markedly delay anagen, while L-type channel blockers act through Ca v 1.2 to induce anagen and overcome the TS phenotype. Ca v 1.2 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.
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Timothy Syndrome-causing point mutations in CACNA1C disrupt development of neuronal dendrites, bone, and skin, and also affect ongoing electrical function in heart and brain.
“For example, point mutations in CACNA1C that underlie Timothy Syndrome perturb the development of neuronal dendrites (Krey and Dolmetsch, 2007), bones (Ramachandran et al., 2013), and skin (Yucel et al., 2013), as well as ongoing electrophysiological function of heart and brain (Krey and Dolmetsch, 2007; Splawski et al., 2005; Splawski et al., 2004).”
From Unifying Views of Autism Spectrum Disorders: A Consideration of Autoregulatory Feedback Loops (2016) · cites this paper as Yucel et al., 2013
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- Authors
- Yucel, G., Altindag, B., Gomez-Ospina, N., Rana, A., Panagiotakos, G., Lara, M. F., Dolmetsch, R., & Oro, A. E.
- Affiliations
- Stanford Medicine (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2013-06-01
- Volume
- 27
- Issue
- 11
- Pages
- 1217-1222
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC3690395
- OpenAlex
- W2040707884
- Cited by
- 31
- References
- 32
- Citations by year
- 2026: 3 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 4 · 2017: 2 · 2016: 1 · 2015: 5 · 2014: 5 · 2013: 1
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- California Institute for Regenerative Medicine
- National Institutes of Health
- National Institute of General Medical Sciences (F32GM090538)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR052785, AR052785)
- Topics
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- Cav1.2, voltage-gated calcium channels, hair follicle stem cells, Timothy syndrome, anagen, L-type calcium channel blockers, BMP signaling, stem cell quiescence, hair follicle regeneration, hair loss
- MeSH terms
- Animals, Autistic Disorder, Calcium, Calcium Channel Blockers, Long QT Syndrome, Stem Cells, Syndactyly, Hair Follicle, Calcium Signaling, Calcium Channels, L-Type, Follistatin-Related Proteins, Mice
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