IQ‐ArfGEF/BRAG1 is associated with synaptic ribbons in the mouse retina

Katsumata, Osamu; Ohara, Naoki; Tamaki, Hideaki; Niimura, Tomoko; Naganuma, Hideaki; Watanabe, Masahiko; Sakagami, Hiroyuki

doi:10.1111/j.1460-9568.2009.06943.x

Cited by 17 publications

(22 citation statements)

References 39 publications

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“…Next, we analyzed the impact of DJ-1 absence on the OPL by labeling the mouse retinas with ribeye/CtBP2, a major structural protein of synaptic ribbons (Katsumata et al, 2009). The OPL from both 3-month- (Fig.…”

Section: Resultsmentioning

confidence: 99%

Loss of DJ-1 elicits retinal abnormalities, visual dysfunction, and increased oxidative stress in mice

Bonilha

Bell

Rayborn

et al. 2015

Experimental Eye Research

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DJ-1/PARK7 mutations or deletions cause autosomal recessive early onset Parkinson’s disease (PD). Thus, DJ-1 protein has been extensively studied in brain and neurons. PD patients display visual symptoms; however, the visual symptoms specifically attributed to PD patients carrying DJ-1/PARK7 mutations are not known. In this study, we analyzed the structure and physiology of retinas of 3- and 6-month-old DJ-1 knockout (KO) mice to determine how loss of function of DJ-1 specifically contributes to the phenotypes observed in PD patients. As compared to controls, the DJ-1 KO mice displayed an increase in the amplitude of the scotopic ERG b-wave and cone ERG, while the amplitude of a subset of the dc-ERG components were decreased. The main structural changes in the DJ-1 KO retinas were found in the outer plexiform layer (OPL), photoreceptors and retinal pigment epithelium (RPE), which were observed at 3 months and progressively increased at 6 months. RPE thinning and structural changes within the OPL were observed in the retinas in DJ-1 KO mice. DJ-1 KO retinas also exhibited disorganized outer segments, central decrease in red/green cone opsin staining, decreased labeling of ezrin, broader distribution of ribeye labeling, decreased tyrosine hydroxylase in dopaminergic neurons, and increased 7,8- dihydro-8-oxoguanine-labeled DNA oxidation. Accelerated outer retinal atrophy was observed in DJ-1 KO mice after selective oxidative damage induced by a single tail vein injection of NaIO3, exposing increased susceptibility to oxidative stress. Our data indicate that DJ-1-deficient retinas exhibit signs of morphological abnormalities and physiological dysfunction in association with increased oxidative stress. Degeneration of RPE cells in association with oxidative stress is a key hallmark of age-related macular degeneration (AMD). Therefore, in addition to detailing the visual defects that occur as a result of the absence of DJ-1, our data is also relevant to AMD pathogenesis.

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Section: Resultsmentioning

confidence: 99%

Loss of DJ-1 elicits retinal abnormalities, visual dysfunction, and increased oxidative stress in mice

Bonilha

Bell

Rayborn

et al. 2015

Experimental Eye Research

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“…Curiously, IQSEC2 transcripts are localised in both hippocampal neuronal cell bodies and dendritic processes, 9 suggesting that local translation of IQSEC2 mRNA in an activity-dependent manner could contribute to synaptic plasticity. Other binding partners 10,11 include a 53 kDa insulin receptor tyrosine kinase substrate IRSp53 and RIBEYE, a unique scaffolding protein found at retinal ribbon synapses. The IQSEC2 protein contains an IQ-like domain, a Sec7 domain, a PH domain and a C-terminal PDZ domain binding motif (fig.…”

Section: Mutations In Iqsec2 Cause Xlidmentioning

confidence: 99%

Subtle functional defects in the Arf-specific guanine nucleotide exchange factor IQSEC2 cause non-syndromic X-linked intellectual disability

Shoubridge

Walikonis²,

Gécz

et al. 2010

Small GTPases

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and robert.harvey@pharmacy.ac.uk m utations in IQSEC2, a guanine nucleotide exchange factor for the adp-ribosylation factor (arf) family of small Gtpases have recently been shown to cause non-syndromic x-linked intellectual disability (id), characterised by substantial limitations in intellectual functioning and adaptive behaviour. this discovery was revealed by a combination of large-scale resequencing of the x chromosome, and key functional assays that revealed a reduction, but not elimination, of iqsEc2 GEf activity for mutations affecting conserved amino acids in the iq-like and sec7 domains. compromised Gtp binding activity of iqsEc2 leading to reduced activation of selected arf substrates (arf1, arf6) is expected to impact on cytoskeletal organization, dendritic spine morphology and synaptic organisation. this study highlights the need for further investigation of the iqsEc gene family and arf Gtpases in neuronal morphology and synaptic function, and suggests that the genes encoding the arfGEfs iqsEc1 and iqsEc3 should be considered as candidates for screening in autosomal id. IntroductionIntelligence describes the ability of the brain to comprehend, infer, make decisions, reason, use language, learn and plan. These cognitive abilities require the correct assembly of complex neuronal structures during development and a continued ability to adapt in response to internal and external cues. Disruption of subtle functional defects in the arf-specific guanine nucleotide exchange factor iqsEc2 cause non-syndromic x-linked intellectual disability

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“…To date, several proteins have been localized to the synaptic ribbon: CtBP1/BARS, the kinesin subunit KIF3A, RIM1 and RIM2, Munc13s, CASTs/ERCs/ ELKS, Piccolo and Bassoon, L-type calcium channels, BRAG1 and RIBEYE (Brandstatter et al, 1999; Muresan et al, 1999; Schmitz et al, 2000; Dick et al, 2001, 2003; Prescott & Zenisek, 2005; tom Dieck et al, 2005; Katsumata et al, 2009; Zanazzi & Matthews, 2009). Of these proteins, only RIBEYE has been found to be unique to the synaptic ribbon.…”

Section: Introductionmentioning

confidence: 99%

High-Resolution Optical Imaging of Zebrafish Larval Ribbon Synapse Protein RIBEYE, RIM2, and CaV 1.4 by Stimulation Emission Depletion Microscopy

Gould

Bewersdorf

et al. 2012

Microsc Microanal

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The synaptic ribbon is a unique presynaptic structure with an intricate morphology in photoreceptors. Because of the resolution limit in conventional fluorescence microscopy, investigating ribbon protein locations has been challenging, especially in the early development stages of model animals. Here, we used stimulated emission depletion microscopy, a super-resolution imaging technique, to look at retina sections in 4 days post-fertilization (dpf) zebrafish. We observed that in photoreceptor cells, RIBEYE and RIM2 are expressed along the synaptic ribbon, with RIM2 consistently located inside of the horseshoe-shaped synaptic ribbon structure with RIBEYE located on the outside. The L-type calcium channel subunit, CACNA1F, exhibited small spot-like staining beneath the RIM2 and RIBEYE structures. Using morpholino antisense oligonucleotides to knock down RIBEYE expression, we observed fewer and shorter ribbons in the photoreceptor outer plexiform layers of 4 dpf fish retina as well as a reduction in RIM2 expression. The clustering of CACNA1F in these blind fish was no longer observed, but instead showed a diffuse expression in the photoreceptor terminal.

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IQ‐ArfGEF/BRAG1 is associated with synaptic ribbons in the mouse retina

Cited by 17 publications

References 39 publications

Loss of DJ-1 elicits retinal abnormalities, visual dysfunction, and increased oxidative stress in mice

Loss of DJ-1 elicits retinal abnormalities, visual dysfunction, and increased oxidative stress in mice

Subtle functional defects in the Arf-specific guanine nucleotide exchange factor IQSEC2 cause non-syndromic X-linked intellectual disability

High-Resolution Optical Imaging of Zebrafish Larval Ribbon Synapse Protein RIBEYE, RIM2, and CaV 1.4 by Stimulation Emission Depletion Microscopy

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