STRA6 Membrane Protein Introduction

Introduction of STRA6

STRA6 encodes a 75 kDa multi-transmembrane protein (receptor for retinol uptake STRA6) expressed in embryonic and adult tissues with no sequence similarity to any known transporter, channel or receptor. The epithelium that constitutes the blood-tissue barrier expresses a particularly high level of STRA6, including the retinal pigment epithelium (RPE) of the eyes, the ependymal cells of the choroid plexus (CP) in the brain, and Sertoli cells of the testis. Biochemical studies have shown that STRA6 is a long-established cellular receptor for the serum retinol-binding protein 4 (RBP4). The systematic structural analysis determines that STRA6 has 9 transmembrane domains, 5 extracellular domains, and 4 intracellular domains. The domain necessary for binding to RBP is located between transmembrane domains VI and VII. It is shown that STRA6 catalyzes the release of retinol from RBP and promotes the translocation of retinol on the membrane and binding to CRBP1.

Function of STRA6 Membrane Protein

STRA6 is particularly abundantly expressed in the eyes, where it is primarily localized in the basolateral membrane of the retinal pigment epithelium, as well as in the female reproductive organs and placenta. Mutations in the human STRA6 gene are associated with Matthew-Wood Syndrome (MWS), which presents ocular defects ranging from mild microphthalmia to anophthalmia, as well as a range of other developmental abnormalities, including cardiac and pulmonary defects and cognitive deficits. STRA6 acts as a retinoid channel that promotes bidirectional flux of vitamin A between the extracellular and intracellular compartments. During this process, cellular accumulation of vitamin A is driven by the esterification of lecithin: retinol acyltransferase (LRAT). STRA6 missense mutations interfere with intracellular STRA6 protein transport or significantly reduce vitamin A uptake. However, STRA6 knockout mice only show ocular vitamin A deficiency but appeared healthy. The phenotype of these mice is similar to mice lacking the STRA6 ligand RBP4; RBP4 knockout mice show intraocular retinol deficiency and visual impairment.

Fig.1 Schematic representation of the location of key positions in STRA6, whose acute modification blocks the transport of vitamin A by STRA6. The transmembrane topology model of STRA6 is described along with the crystal structure of holo-RBP. The key RBP binding domain is shaded in blue. Transmembrane domains and adjacent regions known as part of the vitamin A transport pore are shaded in orange. Residues whose acute modification hinders vitamin A transport by STRA6 are represented as red circles. (Kawaguchi, 2015)

Application of STRA6 Membrane Protein in Literature

1. Noy N. Vitamin A Transport and Cell Signaling by the Retinol-Binding Protein Receptor STRA6. Sub-cellular biochemistry. 2016, 81: 77-93. PubMed ID: 27830501
   
   

   This article points out that retinol transport and cell signaling in STRA6 are largely interdependent and that both are associated with intracellular vitamin A metabolism.

2. Chen Y., et al. Structure of the STRA6 receptor for retinol uptake. Science. 2016, 353(6302). PubMed ID: 27563101
   
   

   This article suggests that zebrafish STRA6 has an intramembrane and nine transmembrane helices in a complex dimeric assembly, and calmodulin binds tightly to STRA6 in a non-canonical arrangement.

3. Kawaguchi R., et al. Vitamin A Transport Mechanism of the Multitransmembrane Cell-Surface Receptor STRA6. Membranes. 2015, 5(3): 425-53. PubMed ID: 26343735
   
   

   This review summarizes the basic molecular mechanisms mediated by plasma retinol binding protein (RBP) receptors and the various catalytic activities of this receptor and compares this transport system with retinoid transport independent of RBP/STRA6.

4. Amengual J., et al. STRA6 is critical for cellular vitamin A uptake and homeostasis. Human Molecular Genetics. 2014, 23(20): 5402-17. PubMed ID: 24852372
   
   

   This article reveals that STRA6-mediated vitamin A uptake is a necessary regulatory process for vitamin A uptake, suggesting that it may be a true vitamin A transporter, which has important implications for diseases associated with impaired blood vitamin A homeostasis.

5. Terra R., et al. To Investigate the Necessity of STRA6 Upregulation in T Cells during T Cell Immune Responses. Plos One. 2013, 8(12): e82808. PubMed ID: 24391722
   
   

   This article draws three conclusions: (1) the loss of STRA6 in T cells does not affect the immune response of T cells; (2) the uptake of STRA6-independent vitamin A compensates for the lack of STRA6 in lymphoid organs under vitamin A sufficient conditions in mice; (3) Even in the case of adequate vitamin A, STRA6 is essential for the uptake of vitamin A in the eye.

STRA6 Preparation Options

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Reference

1. Kawaguchi R, et al. (2015). Vitamin A Transport Mechanism of the Multitransmembrane Cell-Surface Receptor STRA6. Membranes. 5(3): 425-53. PubMed ID: 26343735.

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