Mutations in a gene encoding a new oxygen-regulated photoreceptor protein cause dominant retinitis pigmentosa

Pierce, Eric A.; Quinn, Tracey; Meehan, Terrence F.; McGee, Terri L.; Berson, Eliot L.; Dryja, Thaddeus P.

doi:10.1038/10305

Cited by 166 publications

(120 citation statements)

References 28 publications

(26 reference statements)

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“…RP is a family of inherited retinal diseases characterized by degeneration of rod photoreceptor cells leading to night blindness, visual field restriction, and eventually complete loss of visual function. Most genes associated with autosomal dominant forms of RP are expressed specifically in rod photoreceptors, including genes associated with phototransduction (RHO, GUCA1B) (33,34), photoreceptor-specific transcription factors (CRX, NRL) (35,36), or structural characteristics specific to photoreceptors (RDS, RP1) (37)(38)(39)(40). Other autosomal dominant RP genes are expressed in heterogeneous tissues including the retina and/or the retinal pigment epithelium, such as pre-mRNA splicing factors PRPF3, PRPF8, and PRPF31 (41-43) and the transmembrane protein SEMA4A (44).…”

Section: Discussionmentioning

confidence: 99%

Carbonic anhydrase XIV deficiency produces a functional defect in the retinal light response

Ogilvie¹,

Ohlemiller

Shah

et al. 2007

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

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Members of the carbonic anhydrase (CA) family play an important role in the regulation of pH, CO 2 , ion, and water transport. CA IV and CA XIV are membrane-bound isozymes expressed in the eye. CA IV immunostaining is limited to the choriocapillaris overlying the retina, whereas CA XIV is expressed within the retina in Müller glial cells and retinal pigment epithelium. Here, we have characterized the physiological and morphological phenotype of the CA IV-null, CA XIV-null, and CA IV/CA XIV-double-null mouse retinas. Flash electroretinograms performed at 2, 7, and 10 months of age showed that the rod/cone a-wave, b-wave, and cone b-wave were significantly reduced (26–45%) in the CA XIV-null mice compared with wild-type littermates. Reductions in the dark-adapted response were not progressive between 2 and 10 months, and no differences in retinal morphology were observed between wild-type and CA XIV-null mice. Müller cells and rod bipolar cells had a normal appearance. Retinas of CA IV-null mice showed no functional or morphological differences compared with normal littermates. However, CA IV/CA XIV double mutants showed a greater deficit in light response than the CA XIV-null retina. Our results indicate that CA XIV, which regulates extracellular pH and pCO 2 , plays an important part in producing a normal retinal light response. A larger functional deficit in the CA IV/CA XIV double mutants suggests that CA IV can also contribute to pH regulation, at least in the absence of CA XIV.

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Section: Discussionmentioning

confidence: 99%

Carbonic anhydrase XIV deficiency produces a functional defect in the retinal light response

Ogilvie¹,

Ohlemiller

Shah

et al. 2007

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

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“…4 B-E, J, and K). In humans, the mutations in the RP1 gene generating deletion of the C-terminal portion of RP1 cause dominant retinitis pigmentosa (12). Interestingly, the intensity of acetylated α-tubulin labeling significantly increased in cells expressing the N-terminal RP1 (RP1-N) construct containing the doublecortin domain, indicating that the cytoplasmic microtubules are more stable in these cells (Fig.…”

Section: Rp1 Induces Ciliary Elongation and Reduces The Effect Of Makmentioning

confidence: 94%

“…The retinitis pigmentosa 1 (RP1) protein is localized specifically in the outer-segment axonemes in photoreceptors, which stabilizes cytosolic microtubules (11). A mutation in human RP1 generating a deletion of the RP1 C-terminal portion causes dominant retinitis pigmentosa (12).…”

mentioning

confidence: 99%

Negative regulation of ciliary length by ciliary male germ cell-associated kinase (Mak) is required for retinal photoreceptor survival

Omori

Chaya

Katoh³

et al. 2010

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

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180

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Cilia function as cell sensors in many organs, and their disorders are referred to as "ciliopathies." Although ciliary components and transport machinery have been well studied, regulatory mechanisms of ciliary formation and maintenance are poorly understood. Here we show that male germ cell-associated kinase (Mak) regulates retinal photoreceptor ciliary length and subcompartmentalization. Mak was localized both in the connecting cilia and outer-segment axonemes of photoreceptor cells. In the Mak-null retina, photoreceptors exhibit elongated cilia and progressive degeneration. We observed accumulation of intraflagellar transport 88 (IFT88) and IFT57, expansion of kinesin family member 3A (Kif3a), and acetylated α-tubulin signals in the Mak-null photoreceptor cilia. We found abnormal rhodopsin accumulation in the Mak-null photoreceptor cell bodies at postnatal day 14. In addition, overexpression of retinitis pigmentosa 1 (RP1), a microtubule-associated protein localized in outer-segment axonemes, induced ciliary elongation, and Mak coexpression rescued excessive ciliary elongation by RP1. The RP1 N-terminal portion induces ciliary elongation and increased intensity of acetylated α-tubulin labeling in the cells and is phosphorylated by Mak. These results suggest that Mak is essential for the regulation of ciliary length and is required for the long-term survival of photoreceptors.

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“…10 RP1 is the protein product of retinitis pigmentosa-1 (RP1). 11,12 Mutations in this gene result in progressive blindness, not only in humans, but also in a mouse model. 13 Recently, an additional member of this protein family, doublecortin kinase 2, has been described, and found to posses MT binding activities.…”

Section: Introductionmentioning

confidence: 99%

The DCX Superfamily 1: Common and Divergent Roles for Members of the Mouse DCX Superfamily

Coquelle¹,

Levy²,

Bergmann³

et al. 2006

Cell Cycle

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The doublecortin-like (DCX) domains serve as protein-interaction platforms. DCX tandem domains appear in the product of the X-linked doublecortin (DCX) gene, in retinitis pigmentosa-1 (RP1), as well as in other gene products. Mutations in the human DCX gene are associated with abnormal neuronal migration, epilepsy, and mental retardation; mutations in RP1 are associated with a form of inherited blindness, while DCDC2 has been associated with dyslectic reading disabilities. Motivated by the possible importance of this gene family, a thorough analysis to detect all family members in the mouse was conducted. The DCX-repeat gene superfamily is composed of eleven paralogs, and we cloned the DCX domains from nine different genes. Our study questioned which functions attributed to the DCX domain, are conserved among the different members. Our results suggest that the proteins with the DCX-domain have conserved and unique roles in microtubule regulation and signal transduction. All the tested proteins stimulated microtubule assembly in vitro. Proteins with tandem repeats stabilized the microtubule cytoskeleton in transfected cells, while those with single repeats localized to actin-rich subcellular structures, or the nucleus. All tested proteins interacted with components of the JNK/MAP-kinase pathway, while only a subset interacted with Neurabin 2, and a nonoverlapping group demonstrated actin association. The sub-specialization of some members due to confined intracellular localization, and protein interactions may explain the success of this superfamily.

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Mutations in a gene encoding a new oxygen-regulated photoreceptor protein cause dominant retinitis pigmentosa

Cited by 166 publications

References 28 publications

Carbonic anhydrase XIV deficiency produces a functional defect in the retinal light response

Carbonic anhydrase XIV deficiency produces a functional defect in the retinal light response

Negative regulation of ciliary length by ciliary male germ cell-associated kinase (Mak) is required for retinal photoreceptor survival

The DCX Superfamily 1: Common and Divergent Roles for Members of the Mouse DCX Superfamily

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