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The Biochemistry of Retinoid Signaling II pp 77–93Cite as

Vitamin A Transport and Cell Signaling by the Retinol-Binding Protein Receptor STRA6

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Part of the book series: Subcellular Biochemistry ((SCBI,volume 81))

Abstract

Vitamin A, retinol, circulates in blood bound to retinol binding protein (RBP). In some tissues, the retinol-RBP complex (holo-RBP) is recognized by a membrane receptor, termed STRA6, which mediates uptake of retinol into cells. Recent studies have revealed that, in addition to serving as a retinol transporter, STRA6 is a ligand-activated cell surface signaling receptor that, upon binding of holo-RBP activates JAK/STAT signaling, culminating in the induction of STAT target genes. It has further been shown that retinol transport and cell signaling by STRA6 are critically interdependent and that both are coupled to intracellular vitamin A metabolism. The molecular mechanism of action of STRA6 and its associated machinery is beginning to be revealed, but further work is needed to identify and characterize the complete range of genes and associated signaling cascades that are regulated by STRA6 in different tissues. An understanding of STRA6 is clinically relevant, as for example, it has been shown to be hyper- activated in obese animals, leading to insulin resistance. A potential role for STRA6 in other pathologies, including cancer, awaits further investigation.

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Abbreviations

CRBP:

cellular retinol-binding protein

JAK:

Janus kinases

LRAT:

lecithin:retinol acyltransferase

RA:

retinoic acid

RBP:

serum retinol-binding protein

RPE:

retinal pigment epithelium

SOCS:

suppressor of cytokine signaling

STAT:

signal transducers and activators of transcription

STRA6:

stimulated by retinoic acid 6

TTR:

transthyretin

VAD:

vitamin A-deficient

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Acknowledgements

Work in the author’s laboratory was supported by NIH grants RO1 DK060684, RO1 DK088669, and R01 CA166955

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  1. Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA

    Noa Noy

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  1. Tennessee State University, Nashville, Tennessee, USA

    Mary Ann Asson-Batres

  2. Functional Genomics & Cancer, Institut de Genetique et de Department Functional Genomics & Cancer, Illkirch, France

    Cecile Rochette-Egly

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Noy, N. (2016). Vitamin A Transport and Cell Signaling by the Retinol-Binding Protein Receptor STRA6. In: Asson-Batres, M., Rochette-Egly, C. (eds) The Biochemistry of Retinoid Signaling II. Subcellular Biochemistry, vol 81. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-0945-1_3

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