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Characterization of Ca2+-binding protein 5 knockout mouse retina.

ABSTRACT: The goal of this study was to investigate, with the use of CaBP5 knockout mice, whether Ca(2+)-binding protein 5 (CaBP5) is required for vision. The authors also tested whether CaBP5 can modulate expressed Ca(v)1.2 voltage-activated calcium channels.CaBP5 knockout (Cabp5(-/-)) mice were generated. The retinal morphology and visual function of 6-week-old Cabp5(-/-) mice were analyzed by confocal and electron microscopy, single-flash electroretinography, and whole-cell patch-clamp recordings of retinal ganglion cells. The interaction and modulation of Ca(v)1.2 channels by CaBP5 were analyzed using affinity chromatography, gel overlay assays, and patch-clamp recordings of transfected HEK293 cells.No evidence of morphologic changes and no significant difference in the amplitude of the ERG responses were observed in CaBP5 knockout mice compared with wild-type mice. However, the sensitivity of retinal ganglion cell light responses was reduced by approximately 50% in Cabp5(-/-) mice. CaBP5 directly interacted with the CaM-binding domain of Ca(v)1.2 and colocalized with Ca(v)1.2 in rod bipolar cells. In transfected HEK293T cells, CaBP5 suppressed calcium-dependent inactivation of Ca(v)1.2 and shifted the voltage dependence of activation to more depolarized membrane potentials.This study provides evidence that lack of CaBP5 results in reduced sensitivity of rod-mediated light responses of retinal ganglion cells, suggestive of a role for CaBP5 in the normal transmission of light signals throughout the retinal circuitry. The interaction, colocalization, and modulation of Ca(v)1.2 by CaBP5 suggest that CaBP5 can alter retinal sensitivity through the modulation of voltage-gated calcium channels.

SUBMITTER: Rieke F

PROVIDER: S-EPMC2804972 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

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Characterization of Ca2+-binding protein 5 knockout mouse retina.

Rieke Fred F Lee Amy A Haeseleer Françoise F

Investigative ophthalmology & visual science 20080627 11

<h4>Purpose</h4>The goal of this study was to investigate, with the use of CaBP5 knockout mice, whether Ca(2+)-binding protein 5 (CaBP5) is required for vision. The authors also tested whether CaBP5 can modulate expressed Ca(v)1.2 voltage-activated calcium channels.<h4>Methods</h4>CaBP5 knockout (Cabp5(-/-)) mice were generated. The retinal morphology and visual function of 6-week-old Cabp5(-/-) mice were analyzed by confocal and electron microscopy, single-flash electroretinography, and whole-c ...[more]

PMID: 18586882

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Project description:Quaking (QKI), which belongs to the STAR family of KH domain-containing RNA-binding proteins, functions in pre-mRNA splicing, microRNA regulation, and formation of circular RNA. QKI plays critical roles in myelinogenesis in the central and peripheral nervous systems and has been implicated neuron-glia fate decision in the brain; however, neither the expression nor function of QKI in the neural retina is known. Here we report the expression of QKI RNA-binding protein in the developing and mature mouse retina. QKI was strongly expressed by Müller glial cells in both the developing and adult retina. Intriguingly, during development, QKI was expressed in early differentiating neurons, such as the horizontal and amacrine cells, and subsequently in later differentiating bipolar cells, but not in photoreceptors. Neuronal expression was uniformly weak in the adult. Among QKI isoforms (5, 6, and 7), QKI-5 was the predominantly expressed isoform in the adult retina. To study the function of QKI in the mouse retina, we examined quakingviable(qkv) mice, which have a dysmyelination phenotype that results from deficiency of QKI expression and reduced numbers of mature oligodendrocytes. In homozygous qkv mutant mice (qkv/qkv), the optic nerve expression levels of QKI-6 and 7, but not QKI-5 were reduced. In the retina of the mutant homozygote, QKI-5 levels were unchanged, and QKI-6 and 7 levels, already low, were also unaffected. We conclude that QKI is expressed in developing and adult Müller glia. QKI is additionally expressed in progenitors and in differentiating neurons during retinal development, but expression weakened or diminished during maturation. Among QKI isoforms, we found that QKI-5 predominated in the adult mouse retina. Since Müller glial cells are thought to share properties with retinal progenitor cells, our data suggest that QKI may contribute to maintaining retinal progenitors prior to differentiation into neurons. On the other hand, the expression of QKI in different retinal neurons may suggest a role in neuronal cell type specific fate determination and maturation. The data raises the possibility that QKI may function in retinal cell fate determination and maturation in both glia and neurons.

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Characterization of Ca2+-binding protein 5 knockout mouse retina.

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Characterization of Ca2+-binding protein 5 knockout mouse retina.

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