Retinoic acid receptors and cellular retinoid binding proteins. III. Their differential transcript distribution during mouse nervous system development

Development ◽  
1993 ◽  
Vol 118 (1) ◽  
pp. 267-282 ◽  
Author(s):  
E. Ruberte ◽  
V. Friederich ◽  
P. Chambon ◽  
G. Morriss-Kay
Keyword(s):  
Nervous System ◽  
Retinoic Acid ◽  
Nuclear Receptors ◽  
Binding Proteins ◽  
Binding Protein ◽  
Retinoic Acid Receptors ◽  
Type I ◽  
Crabp I ◽  
Retinoid Binding Proteins ◽  
Crabp Ii

We have studied the transcript distribution of the retinoic acid receptors (RARs) and the cytoplasmic retinoid binding proteins during embryonic development of the mouse nervous system. Of the three retinoic acid receptors, only RAR-gamma was not expressed in developing neural structures. RAR-beta and RAR-alpha both showed rostral limits of expression in the medulla oblongata equivalent to their patterns of expression in the neuroepithelium of the early hindbrain neural tube. Within their expression domains in the spinal cord and brain, RAR-alpha was ubiquitously expressed, whereas RAR-beta transcripts showed very specific patterns of expression, suggesting that this receptor is involved in mediating retinoic acid-induced gene expression in relation to the development of specific neural structures or pathways. The cytoplasmic binding proteins, cellular retinoic acid binding proteins type I and II (CRABP I and CRABP II) and cellular retinol binding protein type I (CRBP I), were widely distributed in developing neural structures. Their differential spatiotemporal patterns of expression suggest that fine regional control of availability of retinoic acid (RA) to the nuclear receptors plays an important role in organization and differentiation of the nervous system. For instance, expression of CRABP I in the migrating cells that give rise to the olivary and pontine nuclei, which develop abnormally in conditions of retinoid excess, is consistent with observations from a variety of other systems indicating that CRABP I limits the access of RA to the nuclear receptors in normal physiological conditions. Similarly, expression of CRBP I in the choroid plexuses, which develop abnormally in conditions of vitamin A deficiency, is consistent with observations indicating that this binding protein mediates the synthesis of RA in tissues requiring high levels of RA for their normal developmental programme. RAR-beta and CRABP II, which are both RA-inducible, were coexpressed with CRBP I in the choroid plexus and in many other sites, perhaps reflecting the fact that all three genes are RA-inducible. The function of CRABP II is not well understood; its domains of expression showed overlaps with both CRABP I and CRBP I.

Structures of cellular retinoic acid binding proteins I and II in complex with synthetic retinoids

1999 ◽  
Vol 55 (11) ◽  
pp. 1850-1857 ◽  
Author(s):  
Barnali Neel Chaudhuri ◽  
Gerard J. Kleywegt ◽  
Isabelle Broutin-L'Hermite ◽  
Terese Bergfors ◽  
Hans Senn ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Binding Proteins ◽  
Specific Protein ◽  
Binding Affinities ◽  
Cellular Processes ◽  
Crabp I ◽  
Retinoid Binding Proteins ◽  
Retinoic Acid Binding Proteins ◽  
Crabp Ii ◽  
Kinetics Of

Retinoids play important roles in diverse cellular processes including growth, cell differentiation and vision. Many natural and synthetic retinoids are used as drugs in dermatology and oncology. A large amount of data has been accumulated on the cellular activity of different synthetic retinoids. They are stabilized and transported inside the cell cytoplasm by binding and transport proteins, such as cellular retinol-binding proteins and cellular retinoic acid binding proteins (CRABPs). The structures of human CRABP II in complex with two different synthetic retinoids, Ro13-6307 and Ro12-7310 (at 2.1 and 2.0 Å resolution, respectively) and of bovine CRABP I in complex with a retinobenzoic acid, Am80 (at 2.8 Å resolution) are described. The binding affinities of human CRABP I and II for the retinoids studied here have been determined. All these compounds have comparable binding affinities (nanomolar range) for both CRABPs. Apart from the particular interactions of the carboxylate group of the retinoids with specific protein groups, each structure reveals characteristic interactions. Studying the atomic details of the interaction of retinoids with retinoid-binding proteins facilitates the understanding of the kinetics of retinoid trafficking inside the cytoplasm.

Immunolocalization of retinol-binding protein, cellular retinoic acid-binding protein I and retinoid X receptor b in the porcine reproductive tract during the oestrous cycle

2001 ◽  
Vol 13 (6) ◽  
pp. 421 ◽  
Author(s):  
Florian J. Schweigert ◽  
Christiane Siegling
Keyword(s):  
Retinoic Acid ◽  
Nuclear Receptors ◽  
Binding Proteins ◽  
Reproductive Tract ◽  
Binding Protein ◽  
Retinoid X Receptor ◽  
Oestrous Cycle ◽  
Retinol Binding Protein ◽  
Acid Binding Protein ◽  
Retinoid Binding Proteins

Retinoid-binding proteins and nuclear receptors are expressed in the reproductive tissues of different species and their expression is hormonally regulated. In the present study, we demonstrated immunocytochemically the temporal and spatial localization of retinol-binding protein (RBP), cellular retinoic acid-binding protein I (CRABPI) and retinoid X receptor β (RXRβ) in porcine ovary, oviduct and uterus during the oestrous cycle. RBP and CRABPI were localized in the cytoplasm, whereas RXRβ occurred in the nucleus. RBP was not detected in either the ovary or the oviduct at any stage of the oestrous cycle. CRABPI was present in luteal cells of the ovary only during dioestrus and in glandular and ciliated cells of the oviduct during oestrus. In the ovary, RXRβ was always present in granulosa cells and germinal epithelium, with highest levels observed during oestrus. In the uterus, RXRβ was present throughout the cycle in both the endometrium and the myometrium. However, changes in RXRβ were observed in the endometrium, with highest levels observed during dioestrus. RBP and CRABPI could be observed in the endometrium only during dioestrus. The results show that the occurrence of retinoid-binding proteins and nuclear receptors in individual tissues of the reproductive tract are strongly dependent on the stage of the oestrous cycle. In the oviduct, the expression of CRABPI seems to be dependent on oestrogen, whereas in the uterus the expression of RBP and CRABPI is influenced by progesterone. The association of expression in different sections of the reproductive tissues investigated shows that the presence of specific proteins involved in retinoid metabolism was dependent on events associated with ovulation, the migration of the oocyte through the oviduct and the possible implantation of the blastocyst into the uterus.

Defective lens fiber differentiation and pancreatic tumorigenesis caused by ectopic expression of the cellular retinoic acid-binding protein I

Development ◽  
1993 ◽  
Vol 119 (2) ◽  
pp. 363-375
Author(s):  
A.V. Perez-Castro ◽  
V.T. Tran ◽  
M.C. Nguyen-Huu
Keyword(s):  
Retinoic Acid ◽  
Binding Proteins ◽  
Binding Protein ◽  
Ectopic Expression ◽  
Retinoic Acid Receptors ◽  
Acid Binding Protein ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Retinoic Acid Binding Proteins

All-trans retinoic acid, a metabolite of retinol, is a possible morphogen in vertebrate development. Two classes of cellular proteins, which specifically bind all-trans retinoic acid, are thought to mediate its action: the nuclear retinoic acid receptors (RAR alpha, beta, gamma), and the cytoplasmic binding proteins known as cellular retinoic acid-binding proteins I and II (CRABP I and II). The function of the retinoic acid receptors is to regulate gene transcription by binding to DNA in conjunction with the nuclear retinoid X receptors (RXR alpha, beta, gamma), which in turn have 9-cis retinoic acid as a ligand. Several lines of evidence suggest that the role of the cellular retinoic acid-binding proteins is to control the concentration of free retinoic acid reaching the nucleus in a given cell. Here, we have addressed the role of the cellular retinoic acid-binding protein I in development by ectopically expressing it in the mouse lens, under the control of the alpha A-crystallin promoter. We show that this ectopic expression interferes with the development of the lens and with the differentiation of the secondary lens fiber cells, causing cataract formation. These results suggest that correct regulation of intracellular retinoic acid concentration is required for normal eye development. In addition, the generated transgenic mice also present expression of the transgene in the pancreas and develop pancreatic carcinomas, suggesting that overexpression of the cellular retinoic acid-binding protein is the cause of the tumors. These results taken together provide evidence for a role of the cellular retinoic acid-binding protein in development and cell differentiation. The relevance of these findings to the possible role of the cellular retinoic acid-binding proteins in the transduction of the retinoic acid signal is discussed.

scholarly journals Expression of cellular retinoic acid-binding protein I and II (CRABP I and II) in embryonic mouse hearts treated with retinoic acid.

2011 ◽  
Vol 58 (1) ◽  
Author(s):  
Emilia Stachurska ◽  
Agnieszka Loboda ◽  
Justyna Niderla-Bielińska ◽  
Małgorzata Szperl ◽  
Michał Juszyński ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Heart Development ◽  
Binding Proteins ◽  
Time Window ◽  
Endocardial Cushions ◽  
Western Blots ◽  
Embryonic Mouse ◽  
Crabp I ◽  
Retinoic Acid Binding Proteins ◽  
Crabp Ii

Cellular retinoic acid binding proteins are considered to be involved in retinoic acid (RA) signaling pathways. Our aim was to compare the expression and localization of cellular retinoic acid binding proteins I and II (CRABP I and II) in embryonic mouse hearts during normal development and after a single teratogenic dose of RA. Techniques such as real-time PCR, RT-PCR, Western blots and immunostaining were employed to examine hearts from embryos at 9-17 dpc. RA treatment at 8.5dpc affects production of CRABP I and II in the heart in the 48-h period. Changes in expression of mRNA for retinaldehyde dehydrogenase II (Raldh2), Crabp1 and Crabp2 genes also occur within the same time window (i.e. 10-11dpc) after RA treatment. In the embryonic control heart these proteins are localized in groups of cells within the outflow tract (OT), and the atrioventricular endocardial cushions. A gradient of labeling is observed with CRABP II but not for CRABP I along the myocardium of the looped heart at 11 dpc; this gradient is abolished in hearts treated with RA, whereas an increase of RALDH2 staining has been observed at 10 dpc in RA-treated hearts. Some populations of endocardial endothelial cells were intensively stained with anti-CRABP II whereas CRABP I was negative in these structures. These results suggest that CRABP I and II are independently regulated during heart development, playing different roles in RA signaling, essential for early remodeling of the heart tube and alignment of the great arteries to their respective ventricles.

Overexpression of Cellular Retinoic Acid-Binding Protein Type II (CRABP-II) and Down-Regulation of CRABP-I in Psoriatic Skin

Dermatology ◽  
1992 ◽  
Vol 185 (4) ◽  
pp. 251-256 ◽  
Author(s):  
G. Siegenthaler ◽  
I. Tomatis ◽  
L. Didierjean ◽  
S. Jaconi ◽  
J.-H. Saurat
Keyword(s):  
Retinoic Acid ◽  
Binding Protein ◽  
Psoriatic Skin ◽  
Type Ii ◽  
Down Regulation ◽  
Acid Binding Protein ◽  
Crabp I ◽  
Crabp Ii

scholarly journals Novel retinoid-binding proteins from filarial parasites

1985 ◽  
Vol 232 (2) ◽  
pp. 577-583 ◽  
Author(s):  
B P Sani ◽  
A Vaid ◽  
J C Comley ◽  
J A Montgomery
Keyword(s):  
Retinoic Acid ◽  
Binding Proteins ◽  
Specific Binding ◽  
Binding Protein ◽  
Gel Filtration ◽  
Retinol Binding Protein ◽  
Acid Binding Protein ◽  
Ligand Interactions ◽  
Avian Origin ◽  
Retinoid Binding Proteins

The present study deals with the discovery and partial characterization of specific binding proteins for retinol and retinoic acid from filarial parasites (worms of the superfamily Filarioidea), including those from two species of Onchocerca. These binding proteins, which are distinct in their physicochemical properties and in the mode of ligand interactions from the host-tissue retinoid-binding proteins, may be involved in the mediation of the putative biological roles of retinoids in the control of parasitic growth, differentiation and reproduction. Parasite retinol-binding protein and retinoic acid-binding protein exhibited specificity for binding retinol and retinoic acid respectively. Both the binding proteins showed an s20,w value of 2.0 S. On gel filtration, both proteins were retarded to a position corresponding to the same molecular size (19.0 kDa). On preparative columns, the parasite binding proteins exhibited isoelectric points at pH 5.7 and 5.75. Unlike the retinoid-binding proteins of mammalian and avian origin, the parasite retinoid-binding proteins showed a lack of mercurial sensitivity in ligand binding. The comparative amounts of retinoic acid-binding protein in five parasites, Onchocerca volvulus, Onchocerca gibsoni, Dipetalonema viteae, Brugia pahangi and Dirofilaria immitis, were between 2.7 and 3.1 pmol of retinoic acid bound/mg of extractable protein. However, the levels of parasite retinol-binding protein were between 4.8 and 5.8 pmol/mg, which is considerably higher than the corresponding levels of cellular retinol-binding protein of mammalian and avian origin. Both retinol- and retinoic acid-binding-protein levels in O. volvulus-infected human nodules and O. gibsoni-infected bovine nodules were similar to their levels in mammalian tissues. Also, these nodular binding proteins, like the host-binding proteins, exhibited mercurial sensitivity to ligand interactions.

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