PUBLICATION
RBP4 Disrupts Vitamin A Uptake Homeostasis in a STRA6-Deficient Animal Model for Matthew-Wood Syndrome
- Authors
- Isken, A., Golczak, M., Oberhauser, V., Hunzelmann, S., Driever, W., Imanishi, Y., Palczewski, K., and von Lintig, J.
- ID
- ZDB-PUB-080309-28
- Date
- 2008
- Source
- Cell Metabolism 7(3): 258-268 (Journal)
- Registered Authors
- Driever, Wolfgang
- Keywords
- none
- MeSH Terms
-
- Mice
- Cardiovascular Abnormalities/embryology
- Cardiovascular Abnormalities/metabolism
- Morpholines/metabolism
- Homeostasis
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Abnormalities, Multiple/genetics
- Abnormalities, Multiple/metabolism*
- Humans
- Disease Models, Animal
- Tretinoin/metabolism
- Animals
- Eye/embryology
- Eye/enzymology
- Eye/metabolism
- Syndrome
- Membrane Proteins/genetics
- Membrane Proteins/metabolism*
- Time Factors
- Oligonucleotides, Antisense/metabolism
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/metabolism*
- NIH 3T3 Cells
- Acyltransferases/metabolism
- Gene Expression Regulation, Developmental
- Transduction, Genetic
- Gene Deletion
- Vitamin A/metabolism*
- Craniofacial Abnormalities/embryology
- Craniofacial Abnormalities/metabolism
- Retinol-Binding Proteins, Plasma/genetics
- Retinol-Binding Proteins, Plasma/metabolism*
- PubMed
- 18316031 Full text @ Cell Metab.
- CTD
- 18316031
Citation
Isken, A., Golczak, M., Oberhauser, V., Hunzelmann, S., Driever, W., Imanishi, Y., Palczewski, K., and von Lintig, J. (2008) RBP4 Disrupts Vitamin A Uptake Homeostasis in a STRA6-Deficient Animal Model for Matthew-Wood Syndrome. Cell Metabolism. 7(3):258-268.
Abstract
The cellular uptake of vitamin A from its RBP4-bound circulating form (holo-RBP4) is a homeostatic process that evidently depends on the multidomain membrane protein STRA6. In humans, mutations in STRA6 are associated with Matthew-Wood syndrome, manifested by multisystem developmental malformations. Here we addressed the metabolic basis of this inherited disease. STRA6-dependent transfer of retinol from RBP4 into cultured NIH 3T3 fibroblasts was enhanced by lecithin:retinol acyltransferase (LRAT). The retinol transfer was bidirectional, strongly suggesting that STRA6 acts as a retinol channel/transporter. Loss-of-function analysis in zebrafish embryos revealed that Stra6 deficiency caused vitamin A deprivation of the developing eyes. We provide evidence that, in the absence of Stra6, holo-Rbp4 provokes nonspecific vitamin A excess in several embryonic tissues, impairing retinoic acid receptor signaling and gene regulation. These fatal consequences of Stra6 deficiency, including craniofacial and cardiac defects and microphthalmia, were largely alleviated by reducing embryonic Rbp4 levels by morpholino oligonucleotide or pharmacological treatments.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping