An Alternative Retinoic Acid-responsive Stra6 Promoter Regulated in Response to Retinol Deficiency

Laursen, Kristian B.; Kashyap, Vasundhra; Scandura, Joseph M.; Gudas, Lorraine J.

doi:10.1074/jbc.m114.613968

Cited by 25 publications

(21 citation statements)

References 50 publications

(47 reference statements)

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“…This down‐regulation is likely caused by the retinoic acid responsiveness of Stra6 mRNA expression in these tissues (14, 15). A recent study confirmed this regulation at the promoter level (32).…”

Section: Discussionmentioning

confidence: 56%

“…To test this hypothesis in live animals, we employed a Stra6 ‐/‐ mouse model that we previously established (15). Because Stra6 mRNA splice variants exist and there is evidence that Stra6 is expressed from different promoters (32), we first confirmed a STRA6‐null phenotype in our animals by employing a commercial polyclonal antibody. This antibody was generated against full‐length human STRA6 and should detect different splice variants.…”

Section: Resultsmentioning

confidence: 71%

“…TaqMan Fast Univ PCR Master Mix (2×) No AmpErase UNG (Applied Biosystems) was used according to manufacturer instructions. Of note, the probe set used for quantitative RT‐PCR of STRA6 sequences does not distinguish between the full Stra6 transcript and the proposed Stra6 alternate transcripts that may derive from alternative splicing (32). Reactions were carried out by using 50 ng cDNA/ 10 μl reaction mixture.…”

Section: Methodsmentioning

confidence: 99%

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Transport of vitamin A across blood‐tissue barriers is facilitated by STRA6

et al. 2016

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Vitamin A bound to retinol binding protein 4 (RBP4) constitutes the major transport mode for retinoids in fasting circulation. Emerging evidence suggests that membrane protein, STRA6 (stimulated by retinoic acid 6), is the RBP4 receptor and vitamin A channel; however, the role of STRA6 in vitamin A homeostasis remains to be defined in vivo. We subjected Stra6-knockout mice to diets sufficient and insufficient for vitamin A and used heterozygous siblings as controls. We determined vitamin A levels of the eyes, brain, and testis, which highly express Stra6, as well as of tissues with low expression, such as lung and fat. We also studied the consequence of STRA6 deficiency on retinoid-dependent processes in tissues. Furthermore, we examined how STRA6 deficiency affected retinoid homeostasis of the aging mouse. The picture that emerged indicates a critical role for STRA6 in the transport of vitamin A across blood-tissue barriers in the eyes, brain, and testis. Concurrently, fat and lung rely on dietary vitamin A. In testis and brain, Stra6 expression was regulated by vitamin A. In controls, this regulation reduced vitamin A consumption when the dietary supply was limited, sequestering it for the eye. Thus, STRA6 is critical for vitamin A homeostasis and the adaption of this process to the fluctuating supply of the vitamin.

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Section: Discussionmentioning

confidence: 56%

Section: Resultsmentioning

confidence: 71%

Section: Methodsmentioning

confidence: 99%

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Transport of vitamin A across blood‐tissue barriers is facilitated by STRA6

et al. 2016

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“…In the eye, mouse Mitf isoforms are known to be differentially regulated during the formation of the RPE (Bharti et al, 2008). We show here that the expression of MITF-A, the second most abundant isoform in human melanocytes (Figure 1 increased expression of Stra6 S from the intronic promoter (Laursen, Kashyap, Scandura, & Gudas, 2015). Similarly, it is conceivable that levels of retinoids may dictate MITF isoform expression within the RPE, as retinoids are known regulators of eye development.…”

Section: Discussionmentioning

confidence: 57%

Delineating the role of MITF isoforms in pigmentation and tissue homeostasis

Flesher

Paterson‐Coleman

Vasudeva

et al. 2019

Pigment Cell Melanoma Res

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MITF, a gene that is mutated in familial melanoma and Waardenburg syndrome, encodes multiple isoforms expressed from alternative promoters that share common coding exons but have unique amino termini. It is not completely understood how these isoforms influence pigmentation in different tissues and how the expression of these independent isoforms of MITF is regulated. Here, we show that melanocytes express two isoforms of MITF, MITF‐A and MITF‐M. The expression of MITF‐A is partially regulated by a newly identified retinoid enhancer element located upstream of the MITF‐A promoter. Mitf‐A knockout mice have only subtle changes in melanin accumulation in the hair and reduced Tyr expression in the eye. In contrast, Mitf‐M‐null mice have enlarged kidneys, lack neural crest‐derived melanocytes in the skin, choroid, and iris stroma, yet maintain pigmentation within the retinal pigment epithelium and iris pigment epithelium of the eye. Taken together, these studies identify a critical role for MITF‐M in melanocytes, a minor role for MITF‐A in regulating pigmentation in the hair and Tyr expression in the eye, and a novel role for MITF‐M in size control of the kidney.

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“…Importantly, RA once formed provides feedforward signaling to upregulate the expression of RARβ which ensures that the levels of RA are consistent with RAR's signaling responses (de The et al, 1990). Through upregulation of CRBP1, STRA6, and RBP4, RA regulates the traffic of retinol in both intra-and extracellular compartments to ensure a stable supply of its precursors (Laursen, Kashyap, Scandura, & Gudas, 2015;Panariello, Quadro, Trematerra, & Colantuoni, 1996;Wei, Blaner, Goodman, & Nguyen-Huu, 1989). Through upregulation of CRBP1, STRA6, and RBP4, RA regulates the traffic of retinol in both intra-and extracellular compartments to ensure a stable supply of its precursors (Laursen, Kashyap, Scandura, & Gudas, 2015;Panariello, Quadro, Trematerra, & Colantuoni, 1996;Wei, Blaner, Goodman, & Nguyen-Huu, 1989).…”

Section: Ra Signaling Gradientsmentioning

confidence: 99%

Recent insights on the role and regulation of retinoic acid signaling during epicardial development

Wang

Moise

2019

Genesis

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The vitamin A metabolite, retinoic acid, carries out essential and conserved roles in vertebrate heart development. Retinoic acid signals via retinoic acid receptors (RAR)/retinoid X receptors (RXRs) heterodimers to induce the expression of genes that control cell fate specification, proliferation, and differentiation. Alterations in retinoic acid levels are often associated with congenital heart defects. Therefore, embryonic levels of retinoic acid need to be carefully regulated through the activity of enzymes, binding proteins and transporters involved in vitamin A metabolism. Here, we review evidence of the complex mechanisms that control the fetal uptake and synthesis of retinoic acid from vitamin A precursors. Next, we highlight recent evidence of the role of retinoic acid in orchestrating myocardial compact zone growth and coronary vascular development.

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An Alternative Retinoic Acid-responsive Stra6 Promoter Regulated in Response to Retinol Deficiency

Cited by 25 publications

References 50 publications

Transport of vitamin A across blood‐tissue barriers is facilitated by STRA6

Transport of vitamin A across blood‐tissue barriers is facilitated by STRA6

Delineating the role of MITF isoforms in pigmentation and tissue homeostasis

Recent insights on the role and regulation of retinoic acid signaling during epicardial development

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