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CRAC channels in dental enamel cells

M Eckstein¹, R S Lacruz¹

¹Dept. Basic Science and Craniofacial Biology, New York University College of Dentistry, 345 East 24th Street, New York 10010, USA.

|August 17, 2018

Summary

Calcium release-activated calcium (CRAC) channels, regulated by STIM1 and ORAI1, are crucial for enamel mineralization. Mutations in these genes cause CRAC channelopathy, leading to enamel defects resembling amelogenesis imperfecta.

Area of Science:

Cellular Biology
Biochemistry
Genetics

Background:

Enamel mineralization depends on calcium ion (Ca2+) availability, primarily facilitated by Ca2+ release-activated Ca2+ (CRAC) channels.
CRAC channels, composed of ORAI1 and regulated by STIM1, control sustained Ca2+ influx essential for biomineralization processes.
Mutations in STIM1 and ORAI1 genes lead to CRAC channelopathy, a group of disorders manifesting with immunodeficiency, muscular hypotonia, ectodermal dysplasia, and abnormal enamel mineralization.

Purpose of the Study:

To review mutations in STIM1 and ORAI1 genes associated with amelogenesis imperfecta (AI)-like phenotypes.
To evaluate enamel defects in CRAC channel-deficient mouse models.
To provide an overview of CRAC channel roles in dentine and bone mineralization.

Main Methods:

Literature review of STIM1 and ORAI1 mutations linked to AI-like phenotypes.
Analysis of enamel defects in CRAC channel-deficient mouse models.
Compilation of existing research on CRAC channels in mineralizing tissues.

Main Results:

STIM1 and ORAI1 mutations are implicated in AI-like enamel defects, affecting both deciduous and permanent teeth.
CRAC channel deficiency in mice results in observable enamel abnormalities.
Dental issues such as discoloration, increased wear, hypoplasia, and chipping are reported in patients with CRAC channelopathy.

Conclusions:

CRAC channels play a critical role in enamel formation, and their dysfunction leads to significant dental abnormalities.
Understanding CRAC channel function is vital for diagnosing and potentially treating genetic disorders affecting enamel mineralization.
Further research into CRAC channels in dentine and bone may reveal broader implications for skeletal health.

Keywords:

Amelogenesis imperfecta CRAC channels Enamel Hypoplasia Mutations

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