DARPP-32 in the ciliary epithelium of the eye: a neurotransmitter-regulated phosphoprotein of brain localizes to secretory cells.

Stone, Richard A.; Laties, Alan M.; Hemmings, HC; Ouimet, Charles C.; Greengard, Paul

doi:10.1177/34.11.2877023

Cited by 37 publications

(15 citation statements)

References 17 publications

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“…In mammals they may well influence intraocular pressure; unfortunately, interpretation of the pressure-effect studies is hampered by their contradictory nature (for review, see ref. 26). Comparable studies are not available for the bird.…”

Section: Resultsmentioning

confidence: 99%

Retinal dopamine and form-deprivation myopia.

Stone

Lin

Laties

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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360

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Investigation of retinal neurochemistry in a well-defined chick model of form-deprivation myopia indicated that dopamine and its metabolite 3,4-dihydroxyphenylacetic acid are reduced in myopic as compared to control eyes. The reduction in retinal dopamine is evident only during light adaptation and is accompanied by a decreased rate ofdopamine biosynthesis. To test whether the alteration in dopamine metabolism is related to eye growth, agents known to interact with dopamine receptors were administered locally to deprived eyes. Remarkably, the expected growth in the axial dimension was reduced, while that in the equatorial dimension was not. Therefore retinal dopamine may participate in the pathway linking visual experience and the postnatal regulation of the eye's growth in the axial dimension. The mechanism for control of chick eye growth in the equatorial dimension remains unknown.Eye growth during normal childhood development coordinates with progressive changes in the optical power of the cornea and lens to maintain image focus on the plane of the retina (1). Observations after unilateral visual deprivation have indicated that retinal image quality influences postnatal growth. Deprivation of form vision in juvenile monkeys (2-4), chicks (5-9), or humans (10-12) disrupts normal regulation and leads to excessive eye size; distant images now focus in front of the retina, causing a myopic refractive error. This link of visual quality to eye size implicates the nervous system in growth control. Moreover, recent observations hint that such control is largely local. (i) Form-deprivation myopia in both monkeys and chicks takes place even after optic nerve transection interrupts the direct pathway from retina to brain (3, 13). (ii) Application of a partial occluder in chicks to restrict vision either in the nasal or temporal visual field induces excessive eye growth only along the corresponding ocular dimension. For example, occlusion of the nasal visual field causes excessive growth of the temporal part of the globe (14-16). We now report in avian myopia that neonatal deprivation of form vision alters retinal dopamine metabolism at the same time as the eye enlarges. Under the identical condition, ocular administration of dopaminerelated agents hinders the expected elongation of the eye in the axial but not in the equatorial dimension. These findings buttress the hypothesis of local growth control and suggest the participation of retinal dopamine in the regulatory sequence. They also speak for separate mechanisms underlying the regulation of axial and equatorial growth of the eye.

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Section: Resultsmentioning

confidence: 99%

Retinal dopamine and form-deprivation myopia.

Stone

Lin

Laties

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

360

323

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“…DARPP-32 has been identified in bovine adipose tissue (this study), ciliary epithelium [21] and brain from a number of species, rat retina, bovine adrenal medulla chromaffin cells, isolated bovine parathyroid cells and choroid plexus [12]. A role for dopamine in regulating the phosphorylation of DARPP-32 has been demonstrated in brain [22] and is postulated in the other tissues in which DARPP-32 is found [23].…”

Section: Sensitivity To Chemical Cleavagementioning

confidence: 99%

“…Protein phosphatase-I is inhibited by nanomolar concentrations of the heat-and acid-stable protein known as inhibitor-1 [l, 21. Inhibitor-1 is active only after it has been phosphorylated on a specific threonine residue by CAMPdependent protein kinase [2].…”

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confidence: 99%

Inhibitors of protein phosphatase‐1

Strålfors¹,

Hemmings²,

Greengard³

1989

European Journal of Biochemistry

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Protein phosphatase inhibitor-1 was purified from bovine adipose tissue. The protein had an apparent molecular mass of 32 kDa by SDSjPAGE and a Stokes' radius of 3.4 nm. It was phosphorylated by CAMPdependent protein kinase on a threonyl residue; this phosphorylation was necessary for inhibition of protein phosphatase-I . Bovine adipose tissue inhibitor-1 was compared directly with rabbit skeletal muscle inhibitor-1 and with a 32 000-M,, dopamine-and CAMP-regulated phosphoprotein from bovine brain (DARPP-32), also an inhibitor of protein phosphatase-1 . By the following biochemical and immunochemical criteria, bovine adipose tissue inhibitor-I was found to be very similar and possibly identical to DARPP-32 and was clearly distinct from skeletal muscle inhibitor-1 : molecular mass by SDS/PAGE; Stokes' radii; phosphorylation on threonine residues; Staphylococcus-aureus-V8-protease-generated peptide patterns analyzed by SDSjPAGE; tryptic phosphopeptide maps analysed by two-dimensional thin-layer electrophoresisjchromatography ; elution on reverse-phase HPLC ; chymotryptic peptide maps as analysed by reverse-phase HPLC; amino acid composition; antibody recognition by immunoprecipitation and immunoblotting; effect of cyanogen bromide cleavage on protein phosphatase inhibitor activity. Based on these results we conclude that bovine brain and adipose tissue contain an identical phosphoprotein inhibitor of protein phosphatase-1 (DARPP-32), which is distinct from that of skeletal muscle (inhibitor-1).

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“…However, DARPP-32-like immunoreactivity has been detected in brown fat cells in pig (15), and the protein has been identified and purified from bovine adipose tissue (16). Previous studies have also identified DARPP-32 in ciliary epithelium (17) and in adrenal chromaffin cells, parathyroid cells, and choroid plexus (13). Evidence has been obtained for the presence of D1-like receptors in several of these tissues (18)(19)(20)(21)(22).…”

mentioning

confidence: 99%

Dopamine- and cAMP-regulated phosphoprotein (DARPP-32) and dopamine DA1 agonist-sensitive Na+,K+-ATPase in renal tubule cells.

Meister

Fryckstedt

Schalling

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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The cellular localization of DARPP-32, a dopamine-and cAMP-regulated phosphoprotein of Mr 32,000 that appears to mediate certain actions of dopamine in the mammalian brain by acting as an inhibitor of protein phosphatase 1, was studied in the kidney of several species. DARPP-32 mRNA and DARPP-32-like inmunoreactivity were found in the cytoplasm of cells in the thick ascending limb of the loop of Henle. The specific dopamine DA, agonist SKF 82526 caused a dose-dependent inhibition ofNa+,K+-ATPase activity, which could be blocked by SCH 23390, a specific DA, antagonist, and by PKI-(5-24) amide, a specific inhibitor of cAMP-dependent protein kinase. The results indicate that DA1 dopamine receptors and DARPP-32, an intracellular third messenger for dopamine, are part of the signal-transduction process for dopamine acting on renal tubule cells.The neurotransmitter dopamine may play an important role in control of renal function. Dopamine is synthesized within the kidney (1) and acts locally to produce natriuresis (2-5) and vasodilation (6). Although these roles for dopamine in kidney physiology are well established, the cellular localization of renal dopamine receptors has not been defined.DARPP-32, a dopamine-and cAMP-regulated phosphoprotein with an apparent molecular weight of 32,000 by SDS/PAGE, has been purified from cytosol of bovine caudate nucleus (7,8). The complete amino acid sequence of bovine brain DARPP-32 has been determined (9), and its cDNA has been isolated and sequenced (10). In the central nervous system, DARPP-32 has been shown to be localized to dopaminoceptive cells containing the D1 dopamine receptor (11,12). It appears to serve as an intracellular third messenger mediating the actions of dopamine at these receptors (7,8,(11)(12)(13). Thus, the phosphorylation of DARPP-32 in intact nerve cells is increased by dopamine acting on D1 receptors, stimulation of adenylate cyclase, formation of cAMP, and stimulation of cAMP-dependent protein kinase (7,8). DARPP-32, in its phosphorylated form, is a potent inhibitor of phosphoprotein phosphatase 1 (14) and has amino acid sequence homology with phosphatase inhibitor 1 (I-1), also an inhibitor of phosphatase 1 (9).DARPP-32 has been analyzed primarily in the central nervous system. However, DARPP-32-like immunoreactivity has been detected in brown fat cells in pig (15), and the protein has been identified and purified from bovine adipose tissue (16). Previous studies have also identified DARPP-32 in ciliary epithelium (17) and in adrenal chromaffin cells, parathyroid cells, and choroid plexus (13). Evidence has been obtained for the presence of D1-like receptors in several of these tissues (18)(19)(20)(21)(22). Thus, DARPP-32 appears to be a useful marker for cells containing the central (D1) and peripheral (DA1) dopamine receptors. In the present study we investigated the cellular localization of DARPP-32 and, for purposes of comparison, I-1, in the kidney. Both proteins were localized in the same cells of a specific portion of the loop of Henle; ...

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DARPP-32 in the ciliary epithelium of the eye: a neurotransmitter-regulated phosphoprotein of brain localizes to secretory cells.

Cited by 37 publications

References 17 publications

Retinal dopamine and form-deprivation myopia.

Retinal dopamine and form-deprivation myopia.

Inhibitors of protein phosphatase‐1

Dopamine- and cAMP-regulated phosphoprotein (DARPP-32) and dopamine DA1 agonist-sensitive Na+,K+-ATPase in renal tubule cells.

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