Calcium selective channel TRPV6: Structure, function, and implications in health and disease

Area of Science:

• Biophysics
• Molecular Biology
• Physiology

Background:

• TRPV6 (Transient Receptor Potential channel family, Vanilloid subfamily member 6) is a calcium-selective channel crucial for transcellular calcium transport.
• Recent structural studies reveal mechanisms of TRPV6 calcium selectivity, permeation, and calmodulin inactivation.
• TRPV6 is expressed in various epithelial tissues and regulated by vitamin D, dietary calcium, and physiological states like pregnancy.

Purpose of the Study:

• To review the current knowledge on TRPV6 expression, structure, biophysical properties, function, and regulation.
• To discuss the implications of TRPV6 polymorphisms and dysfunction in human diseases.
• To highlight the role of TRPV6 in calcium homeostasis and its association with malignancies.

Main Methods:

• Literature review of structural, functional, and genetic studies on TRPV6.
• Analysis of gene expression data and clinical correlations.
• Examination of data from genetic models of TRPV6 loss of function.

Main Results:

• TRPV6 loss-of-function models exhibit hypercalciuria, reduced bone density, impaired fertility, and issues with maternal-fetal calcium transport.
• TRPV6 is overexpressed in many cancers, correlating with aggressiveness, metastasis, and poor survival.
• TRPV6 gene mutations are linked to neonatal hyperparathyroidism and chronic pancreatitis.

Conclusions:

• TRPV6 is essential for calcium homeostasis and male fertility.
• Aberrant TRPV6 expression and function are implicated in diverse human pathologies, including cancer and pancreatitis.
• Further research into TRPV6 is warranted for understanding and treating associated diseases.