The Carboxyl Terminal Domain of Phosducin Functions as a Transcriptional Activator

Zhu, Xuemei; Craft, Cheryl M.

doi:10.1006/bbrc.2000.2414

Cited by 17 publications

(13 citation statements)

References 41 publications

(26 reference statements)

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“…Another hypothesis, also consistent with the reduction of ␤␥ subunits in the rods of phosducin knockout mice, is that phosducin participates in transcriptional regulation (42). This hypothesis is based on the observations that 1) the phosducin C-terminal domain of 40 amino acid residues could serve as a transcriptional activator in both yeast and mammalian cells (42), 2) phosducin interacts with the photoreceptor-specific transcription factor CRX in vitro (43), and 3) a fraction of phosducin is present in the nuclei of bovine rods (27).…”

Section: Discussionsupporting

confidence: 54%

“…This hypothesis is based on the observations that 1) the phosducin C-terminal domain of 40 amino acid residues could serve as a transcriptional activator in both yeast and mammalian cells (42), 2) phosducin interacts with the photoreceptor-specific transcription factor CRX in vitro (43), and 3) a fraction of phosducin is present in the nuclei of bovine rods (27). In the next study using the phosducin knockout mouse we plan to analyze the reduction in transducin ␤␥ subunits in the context of either its reduced synthesis or its enhanced proteolysis.…”

Section: Discussionmentioning

confidence: 99%

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Phosducin Facilitates Light-driven Transducin Translocation in Rod Photoreceptors

Sokolov

Strissel

Leskov

et al. 2004

Journal of Biological Chemistry

108

168

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Phosducin is a photoreceptor-specific protein known to interact with the ␤␥ subunits of G proteins. In pursuit of the function of phosducin, we tested the hypothesis that it regulates the light-driven translocation of G protein transducin from the outer segments of rod photoreceptors to other compartments of the rod cell. Transducin translocation has been previously shown to contribute to rod adaptation to bright illumination, yet the molecular mechanisms underlying the translocation phenomenon remain unknown. In this study we provide two major lines of evidence in support of the role of phosducin in transducin translocation. First, we have demonstrated that transducin ␤␥ subunits interact with phosducin along their entire intracellular translocation route, as evident from their co-precipitation in serial tangential sections from light-adapted but not darkadapted retinas. Second, we generated a phosducin knockout mouse and found that the degree of lightdriven transducin translocation in the rods of these mice was significantly reduced as compared with that observed in the rods of wild type animals. In knockout animals the translocation of transducin ␤␥ subunits was affected to a larger degree than the translocation of the ␣ subunit. We also found that the amount of phosducin in rods is sufficient to interact with practically all of the transducin present in these cells and that the subcellular distribution of phosducin is consistent with that of a soluble protein evenly distributed throughout the entire rod cytoplasm. Together, these data indicate that phosducin binding to transducin ␤␥ subunits facilitates transducin translocation. We suggest that the mechanism of phosducin action is based on the reduction of transducin affinity to the membranes of rod outer segments, achieved by keeping the transducin ␤␥ subunits apart from the ␣ subunit. This increased solubility of transducin would make it more susceptible to translocation from the outer segments.Vertebrate photoreceptors are highly specialized neurons responsible for the reception and primary processing of visual information. The outer segment compartment of the photoreceptor contains large amounts of the proteins involved in light detection and in the generation of the visual signal (for review, see Refs. 1-4). Photons entering the outer segment are absorbed by rhodopsin, which triggers sequential activation of many molecules of the photoreceptor-specific heterotrimeric G protein, transducin. Transducin activation consists of GTP binding to its ␣ subunit followed by dissociation of the ␣ subunit from the transducin ␤␥ subunits and the subsequent stimulation of the downstream effector, cGMP phosphodiesterase. Signaling persists until GTP is hydrolyzed and transducin subunits re-associate into a heterotrimer. In dark-adapted rods most of the transducin is located in the outer segments. However, prolonged exposures to bright light cause massive transducin translocation from rod outer segments to other subcellular compartments of the rod (5-10). In a recent st...

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Phosducin Facilitates Light-driven Transducin Translocation in Rod Photoreceptors

Sokolov

Strissel

Leskov

et al. 2004

Journal of Biological Chemistry

108

168

View full text Add to dashboard Cite

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“…In all amniotes except primates, phosducin has three exons; the last begins in the same place in all amniotes. Our primers match the cAMP-dependent protein kinase (PKA) recognition site at the 5 0 end (Kobayashi et al, 2002), and a conserved region thought to be important for transcriptional regulation at the 3 0 end (Zhu and Craft, 2000). Both the primer sites and the resulting phosducin sequences reported here are all part of the third exon.…”

Section: Dna Extraction Amplification and Sequencingmentioning

confidence: 94%

“…It is expressed in high levels in retinal photoreceptor and pineal cells (Lee et al, 2004). In addition to light-activated dephosphorylation in photoreceptor cells (Kobayashi et al, 2002;Lee et al, 2004), phosducin also has a role as a transcriptional activator (Zhu and Craft, 2000). For the known sequences in amniotes, the number of amino acids varies from 244 in Mus musculus to 249 in Phelsuma madagascariensis.…”

Section: Dna Extraction Amplification and Sequencingmentioning

confidence: 99%

Molecular phylogenetic relationships among species of the Malagasy-Comoran gecko genus Paroedura (Squamata: Gekkonidae)

Jackman¹,

Bauer²,

Greenbaum³

et al. 2008

Molecular Phylogenetics and Evolution

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We use 3100 bp of mitochondrial (ND2, ND4) and nuclear (RAG1, phosducin) DNA sequence data to recover phylogenetic relationships among 14 of the 16 recognized taxa of the lizard genus Paroedura as well as two undescribed forms. These geckos are endemic to Madagascar and the Comores and are popularly kept and bred by herpetoculturalists. The closest relative of Paroedura is another Indian Ocean leaf-toed gecko, Ebenavia. Both Bayesian inference and maximum parsimony strongly support the monophyly of two major clades within Paroedura that conflict with existing species group assignments based on scale characteristics. Our well-resolved tree elucidates a biogeographic pattern in which eastern Paroedura are most basal and western and south-western species form a monophyletic group. Our data demonstrate the phylogenetic utility of phosducin, a novel marker in squamate phylogenetics, at the intrageneric level.

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“…Frameshift mutations of the C-terminal portion of CRX will lead to alteration of the encoded sequence and loss of the OTX tail, which may affect interactions with other factors, e.g. NRL, RX, p300/CBP, and phosducin (3,15,(21)(22)(23)(24).…”

mentioning

confidence: 99%

Functional Domains of the Cone-Rod Homeobox (CRX) Transcription Factor

Chau¹,

Chen²,

Zack³

et al. 2000

Journal of Biological Chemistry

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The paired-like homeodomain transcription factor CRX (cone-rod homeobox) is involved in regulating photoreceptor gene expression and rod outer segment development. Mutations in CRX have been associated with several retinal degenerative diseases. These conditions range from Leber congenital amaurosis (a severe cone and rod degeneration of childhood onset) to adult onset cone-rod dystrophy and retinitis pigmentosa (an adult onset condition that primarily affects rods). The goal of this study is to better understand the molecular basis of CRX function and to provide insight into how mutations in CRX cause such a variety of clinical phenotypes. We performed deletion analysis in conjunction with DNA binding and transient transfection-based transactivation studies to identify the functional domains within CRX. DNA binding requires a complete homeodomain. Furthermore, truncated proteins that did not contain an intact homeodomain failed to demonstrate detectable expression in tissue culture upon transfection. Transactivation analysis indicated that both the OTX tail and the WSP domain are important for controlling positive regulatory activity of CRX. Interestingly, the mapped CRX transactivation domains were also critical when coexpressed with NRL. Specifically, the synergy between CRX and NRL was constant regardless of which CRX variant was used.

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The Carboxyl Terminal Domain of Phosducin Functions as a Transcriptional Activator

Cited by 17 publications

References 41 publications

Phosducin Facilitates Light-driven Transducin Translocation in Rod Photoreceptors

Phosducin Facilitates Light-driven Transducin Translocation in Rod Photoreceptors

Molecular phylogenetic relationships among species of the Malagasy-Comoran gecko genus Paroedura (Squamata: Gekkonidae)

Functional Domains of the Cone-Rod Homeobox (CRX) Transcription Factor

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