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Cited by 316Vitamin D Research StudiesProtein Interaction Studies and Fluorescence AnalysisParathyroid Disorders and Treatments

Vitamin D Binding Protein: A Historic Overview

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Bouillon, Roger, Schuit, Frans, Antonio, Leen, Rastinejad, Fraydoon·2020·Frontiers in Endocrinology
DOI 10.3389/fendo.2019.00910PMC PMC6965021
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Abstract

Vitamin D and all its metabolites are bound to a specific vitamin D binding protein, DBP. This protein was originally first discovered by its worldwide polymorphism and called Group-specific Component (GC). We now know that DBP and GC are the same protein and appeared early in the evolution of vertebrates. DBP is genetically the oldest member of the albuminoid family (including albumin, α-fetoprotein and afamin, all involved in transport of fatty acids or hormones). DBP has a single binding site for all vitamin D metabolites and has a high affinity for 25OHD and 1,25(OH)2D, thereby creating a large pool of circulating 25OHD, which prevents rapid vitamin D deficiency. DBP of higher vertebrates (not amphibians or reptiles) binds with very high affinity actin, thereby preventing the formation of polymeric actin fibrils in the circulation after tissue damage. Megalin is a cargo receptor and is together with cubilin needed to reabsorb DBP or the DBP-25OHD complex, thereby preventing the urinary loss of these proteins and 25OHD. The total concentrations of 25OHD and 1,25(OH)2D in DBP null mice or humans are extremely low but calcium and bone homeostasis remain normal. This is the strongest argument for claiming that the "free hormone hypothesis" also applies to the vitamin D hormone, 1,25(OH)2D. DBP also transports fatty acids, and can play a role in the immune system. DBP is genetically very polymorphic with three frequent alleles (DBP/GC 1f, 1s, and 2) but in total more than 120 different variants but its health consequences, if any, are not understood. A standardization of DBP assays is essential to further explore the role of DBP in physiology and diseases.

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  • Megalin- and cubilin-mediated endocytosis is relevant in vitamin D metabolism, binding and reabsorbing the vitamin D-DBP complex from glomerular ultrafiltrate, preventing uncontrolled loss of vitamin D metabolites in urine.

    “While not applicable to T and SHBG, megalin- and cubilin-mediated endocytosis is, however, relevant in vitamin D metabolism. Being mainly expressed on the luminal brush border membrane of the renal proximal convoluted tubule, megalin and cubilin bind and reabsorb the vitamin D–DBP complex from the glomerular ultrafiltrate, hereby preventing uncontrolled loss of vitamin D metabolites in urine.”

    From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [37]

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Cited by

Sorted by citations

Authors
Bouillon, R., Schuit, F., Antonio, L., & Rastinejad, F.
Affiliations
  • KU Leuven (BE)
  • Universitair Ziekenhuis Leuven (BE)
  • University of Oxford (GB)
Corresponding author
Bouillon, Roger
ORCID
Venue
Frontiers in Endocrinology
Publisher
Frontiers Media SA
Published
2020-01-10
Volume
10
Pages
910-910
ISSN
1664-2392 (ISSN-L)
DOI
10.3389/fendo.2019.00910
PMC
PMC6965021
OpenAlex
W3000631773
Cited by
316
References
4
Citations by year
2026: 25 · 2025: 56 · 2024: 46 · 2023: 50 · 2022: 73 · 2021: 49 · 2020: 16 · 2019: 1
FWCI
7.47
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Endocrinology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Lirias (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Wellcome Trust (210664/Z/18/Z)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
  • Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
Keywords
vitamin D binding protein, group-specific component, vitamin D metabolites, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, actin binding, megalin, cubilin, free hormone hypothesis, fatty acid uptake, immune function

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