Cuimei Liu
Morehouse School of Medicine
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Publication
Featured researches published by Cuimei Liu.
Journal of Neurochemistry | 2005
M.D. Rollag; G. Jiang; W.P. Hayes; Rashidul Haque; A. Natesan; M. Zatz; Gianluca Tosini; Cuimei Liu; Horst-Werner Korf; P. M. Iuvone; I. Provencio
The avian retina and pineal gland contain autonomous circadian oscillators and photo‐entrainment pathways, but the photopigment(s) that mediate entrainment have not been definitively identified. Melanopsin (Opn4) is a novel opsin involved in entrainment of circadian rhythms in mammals. Here, we report the cDNA cloning of chicken melanopsin and show its expression in retina, brain and pineal gland. Like the melanopsins identified in amphibians and mammals, chicken melanopsin is more similar to the invertebrate retinaldehyde‐based photopigments than the retinaldehyde‐based photopigments typically found in vertebrates. In retina, melanopsin mRNA is expressed in cells of all retinal layers. In pineal gland, expression was strong throughout the parenchyma of the gland. In brain, expression was observed in a few discrete nuclei, including the lateral septal area and medial preoptic nucleus. The retina and pineal gland showed distinct diurnal expression patterns. In pineal gland, melanopsin mRNA levels were highest at night at Zeitgeber time (ZT) 16. In contrast, transcript levels in the whole retina reached their highest levels in the early morning (ZT 0–4). Further analysis of melanopsin mRNA expression in retinal layers isolated by laser capture microdissection revealed different patterns in different layers. There was diurnal expression in all retinal layers except the ganglion cell layer, where heavy expression was localized to a small number of cells. Expression of melanopsin mRNA peaked during the daytime in the retinal pigment epithelium and inner nuclear layer but, like in the pineal, at night in the photoreceptors. Localization and regulation of melanopsin mRNA in the retina and pineal gland is consistent with the hypothesis that this novel photopigment plays a role in photic regulation of circadian function in these tissues.
PLOS Biology | 2006
James Bellingham; Zara Melyan; Cuimei Liu; Morven A. Cameron; Emma E. Tarttelin; P. Michael Iuvone; Mark W. Hankins; Gianluca Tosini; Robert J. Lucas
In mammals, the melanopsin gene (Opn4) encodes a sensory photopigment that underpins newly discovered inner retinal photoreceptors. Since its first discovery in Xenopus laevis and subsequent description in humans and mice, melanopsin genes have been described in all vertebrate classes. Until now, all of these sequences have been considered representatives of a single orthologous gene (albeit with duplications in the teleost fish). Here, we describe the discovery and functional characterisation of a new melanopsin gene in fish, bird, and amphibian genomes, demonstrating that, in fact, the vertebrates have evolved two quite separate melanopsins. On the basis of sequence similarity, chromosomal localisation, and phylogeny, we identify our new melanopsins as the true orthologs of the melanopsin gene previously described in mammals and term this grouping Opn4m. By contrast, the previously published melanopsin genes in nonmammalian vertebrates represent a separate branch of the melanopsin family which we term Opn4x. RT-PCR analysis in chicken, zebrafish, and Xenopus identifies expression of both Opn4m and Opn4x genes in tissues known to be photosensitive (eye, brain, and skin). In the day-14 chicken eye, Opn4m mRNA is found in a subset of cells in the outer nuclear, inner nuclear, and ganglion cell layers, the vast majority of which also express Opn4x. Importantly, we show that a representative of the new melanopsins (chicken Opn4m) encodes a photosensory pigment capable of activating G protein signalling cascades in a light- and retinaldehyde-dependent manner under heterologous expression in Neuro-2a cells. A comprehensive in silico analysis of vertebrate genomes indicates that while most vertebrate species have both Opn4m and Opn4x genes, the latter is absent from eutherian and, possibly, marsupial mammals, lost in the course of their evolution as a result of chromosomal reorganisation. Thus, our findings show for the first time that nonmammalian vertebrates retain two quite separate melanopsin genes, while mammals have just one. These data raise important questions regarding the functional differences between Opn4x and Opn4m pigments, the associated adaptive advantages for most vertebrate species in retaining both melanopsins, and the implications for mammalian biology of lacking Opn4x.
Cell and Tissue Research | 2004
Cuimei Liu; Chiaki Fukuhara; James H. Wessel; P. Michael Iuvone; Gianluca Tosini
Arylalkylamine N-acetyltransferase (AA-NAT) is the key regulatory enzyme in the melatonin biosynthetic pathway. Previous investigations have reported that Aa-nat mRNA in rat is only detected in a sub-population of photoreceptor cells that resemble cones in shape and size. In the present study, we investigated Aa-nat expression in the rat retina by using in situ hybridization and laser capture microdissection combined with the reverse transcription/polymerase chain reaction technique. Our results demonstrate that, contrary to previous reports, Aa-nat transcripts are present not only in the photoreceptor cells, but also in the inner nuclear layer and in the ganglion cell layer. However, the rhythmic expression of Aa-nat mRNA was observed only in photoreceptor cells.
Science Signaling | 2013
Kenkichi Baba; Abla Benleulmi-Chaachoua; Anne-Sophie Journé; Maud Kamal; Jean-Luc Guillaume; Sébastien Dussaud; Florence Gbahou; Katia Yettou; Cuimei Liu; Susana Contreras-Alcantara; Ralf Jockers; Gianluca Tosini
Melatonin stimulates a heteromeric G protein–coupled receptor to modulate the eye’s response to light flashes at night. Flash Response In the retina, melatonin increases photoreceptor sensitivity to light at night, but not in mice deficient in the melatonin receptor MT1. Baba et al. found that two melatonin receptors, the G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptors (GPCRs) MT1 and MT2, were both present in the photoreceptor cells of mice, and, when coexpressed in cultured cells, these receptors formed homomeric and heteromeric complexes. Mice deficient in MT2 or expressing a mutant form of MT2 failed to respond to melatonin, suggesting that MT1 and MT2 may function as a heteromeric complex to mediate this response. By testing the response in the presence of various pharmacological agents, melatonin mediated its effect on photoreceptor responses in vivo through the inositol trisphosphate to protein kinase C pathway. Thus, this study delineates a pathway by which melatonin affects vision and provides in vivo evidence for functional GPCR heteromers. The formation of G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptor (GPCR) heteromers enables signaling diversification and holds great promise for improved drug selectivity. Most studies of these oligomerization events have been conducted in heterologous expression systems, and in vivo validation is lacking in most cases, thus questioning the physiological significance of GPCR heteromerization. The melatonin receptors MT1 and MT2 exist as homomers and heteromers when expressed in cultured cells. We showed that melatonin MT1/MT2 heteromers mediated the effect of melatonin on the light sensitivity of rod photoreceptors in mice. This effect of melatonin involved activation of the heteromer-specific phospholipase C and protein kinase C (PLC/PKC) pathway and was abolished in MT1−/− or MT2−/− mice, as well as in mice overexpressing a nonfunctional MT2 mutant that interfered with the formation of functional MT1/MT2 heteromers in photoreceptor cells. Not only does this study establish an essential role of melatonin receptor heteromers in retinal function, it also provides in vivo support for the physiological importance of GPCR heteromerization. Thus, the MT1/MT2 heteromer complex may provide a specific pharmacological target to improve photoreceptor function.
Journal of Neurochemistry | 2004
Katsuhiko Sakamoto; Cuimei Liu; Gianluca Tosini
Previous studies have demonstrated that the mammalian retina contains a circadian clock system that controls several retinal functions. In mammals the location of the retinal circadian clock is unknown whereas, in non‐mammalian vertebrates, earlier work has demonstrated that photoreceptor cells contain the circadian clock. New experimental evidence has suggested that in mammals the retinal circadian clock may be located outside the photoreceptor cells. In this study we report that circadian rhythms in Aa‐nat mRNA (in vivo) and melatonin synthesis (in vitro) are still present in the retina of rats lacking photoreceptors. The circadian pacemaker(s) controlling such rhythms is probably located in kainic acid sensitive neurons in the inner retina since kainic acid injections abolished the rhythmicity. These data are the first direct demonstration that circadian rhythmicity in the mammalian retina can be generated independently from the photoreceptors and the suprachiasmatic nuclei of the hypothalamus.
Brain Research | 2007
Gianluca Tosini; Jacopo Aguzzi; Nicole M. Bullock; Cuimei Liu; Manami Kasamatsu
The study of how the retina processes the photic information required for the entrainment of the circadian system is an exciting new topic in retinal neurobiology. We have recently shown that in RCS/N-rdy rats melanopsin mRNA levels are dramatically reduced (about 90%) and melanopsin immunoreactivity cannot be detected in the retina of these rats at 60 days of age. Although RCS/N-rdy rats are a widely used model to investigate mechanisms of photoreceptor degeneration, no study has investigated circadian photoreception in these animals. The aim of this study was to examine circadian photoreception in RCS/N-rdy(+) (rdy(+)) rats homozygous for the normal rdy allele and age-matched RCS/N-rdy (rdy) homozygotes with retinal dystrophy. No differences between RCS/N-rdy and rdy(+) were observed in light-induced phase shift of locomotor activity at the three light intensities used (1 x 10(-3), 1 x 10(-1), and 1 x 10(1) microW cm(-2)). Surprisingly, we observed that in RCS/N-rdy the free-running period of the circadian rhythm of locomotor activity was shorter (P<0.01) than in rdy(+), thus suggesting that photoreceptor degeneration may affect the free-running period of the locomotor activity rhythm.
Brain Research | 2013
John V.K. Pulliam; Zhenfeng Xu; Gregory D. Ford; Cuimei Liu; Yonggang Li; Kyndra C. Stovall; Virginetta S. Cannon; Teclemichael Tewolde; Carlos S. Moreno; Byron D. Ford
Microarray analysis has been used to understand how gene regulation plays a critical role in neuronal injury, survival and repair following ischemic stroke. To identify the transcriptional regulatory elements responsible for ischemia-induced gene expression, we examined gene expression profiles of rat brains following focal ischemia and performed computational analysis of consensus transcription factor binding sites (TFBS) in the genes of the dataset. In this study, rats were sacrificed 24 h after middle cerebral artery occlusion (MCAO) stroke and gene transcription in brain tissues following ischemia/reperfusion was examined using Affymetrix GeneChip technology. The CONserved transcription FACtor binding site (CONFAC) software package was used to identify over-represented TFBS in the upstream promoter regions of ischemia-induced genes compared to control datasets. CONFAC identified 12 TFBS that were statistically over-represented from our dataset of ischemia-induced genes, including three members of the Ets-1 family of transcription factors (TFs). Microarray results showed that mRNA for Ets-1 was increased following tMCAO but not pMCAO. Immunohistochemical analysis of Ets-1 protein in rat brains following MCAO showed that Ets-1 was highly expressed in neurons in the brain of sham control animals. Ets-1 protein expression was virtually abolished in injured neurons of the ischemic brain but was unchanged in peri-infarct brain areas. These data indicate that TFs, including Ets-1, may influence neuronal injury following ischemia. These findings could provide important insights into the mechanisms that lead to brain injury and could provide avenues for the development of novel therapies.
PLOS Biology | 2006
James Bellingham; Zara Melyan; Cuimei Liu; Morven A. Cameron; Emma E. Tarttelin; P M Iuvone; Mark W. Hankins; Gianluca Tosini; Robert J. Lucas
Investigative Ophthalmology & Visual Science | 2006
James Bellingham; Cuimei Liu; Z. Melyan; Morven A. Cameron; Emma E. Tarttelin; Gianluca Tosini; Mark W. Hankins; P.M. Iuvone; Robert J. Lucas
Investigative Ophthalmology & Visual Science | 2005
Gianluca Tosini; Katsuhiko Sakamoto; Cuimei Liu; Nikita Pozdeyev; P.M. Iuvone