A comparative analysis of rod bipolar cell transcriptomes identifies novel genes implicated in night vision

Woods, Sasha M; Mountjoy, Edward; Muir, Duncan; Ross, Sarah E.; Atan, Denize

doi:10.1038/s41598-018-23901-6

Cited by 14 publications

(30 citation statements)

References 58 publications

(133 reference statements)

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“…Results with CRISPR knockout of LRRTM4, described below, further validate the specificity of LRRTM4 immunostaining. Detection of LRRTM4 in rod BC dendritic tips, but not cone BC tips, is consistent with the observed enrichment of LRRTM4 transcripts specifically in rod BCs (Shekhar et al, 2016;Woods et al, 2018).…”

Section: Lrrtm4 Is Specifically Localized To Rod Bc Dendritic Tipssupporting

confidence: 85%

“…Like ELFN1, LRIT3, and nyctalopin, LRRTM proteins have an LRR-containing extracellular N-terminal domain, a single transmembrane helix, and a Cterminal cytoplasmic domain. LRRs encode a conserved structural motif shaped like a curved solenoid (Barton et al, 2003;Bella, Hindle, McEwan, & Lovell, 2008;Paatero et al, 2016;Yamagata et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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LRRTM4 is a member of the transsynaptic complex between rod photoreceptors and bipolar cells

Agosto

Wensel

2020

J of Comparative Neurology

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Leucine rich repeat transmembrane (LRRTM) proteins are synaptic adhesion molecules with roles in synapse formation and signaling. LRRTM4 transcripts were previously shown to be enriched in rod bipolar cells (BCs), secondary neurons of the retina that form synapses with rod photoreceptors. Using two different antibodies, LRRTM4 was found to reside primarily at rod BC dendritic tips, where it colocalized with the transduction channel protein, TRPM1. LRRTM4 was not detected at dendritic tips of ON-cone BCs. Following somatic knockout of LRRTM4 in BCs by subretinal injection and electroporation of CRISPR/Cas9, LRRTM4 was abolished or reduced in the dendritic tips of transfected cells. Knockout cells had a normal complement of TRPM1 at their dendritic tips, while GPR179 accumulation was partially reduced. In experiments with heterologously expressed protein, the extracellular domain of LRRTM4 was found to engage in heparan-sulfate dependent binding with pikachurin. These results implicate LRRTM4 in the GPR179-pikachurin-dystroglycan transsynaptic complex at rod synapses.

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Section: Lrrtm4 Is Specifically Localized To Rod Bc Dendritic Tipssupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

LRRTM4 is a member of the transsynaptic complex between rod photoreceptors and bipolar cells

Agosto

Wensel

2020

J of Comparative Neurology

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“…This finding is in line with reports from others, who observed increased expression levels of Kcne2 by data from cell-sorted rod-BC bulk RNA-sequencing or single-cell RNA-sequencing. [26][27][28] However, we did not observe a 1:1 overlap of immunoreactivity for Kcne2 and the rod-BC marker PKCα. Rather, Kcne2 immunoreactivity was arranged in U-shaped patterns remotely from the rod-BC somata where PKCα staining is becoming faint.…”

Section: Discussioncontrasting

confidence: 71%

Expression and Localization ofKcne2in the Vertebrate Retina

Lindner

Gilhooley

Palumaa

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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To characterize the retinal expression and localization of Kcne2, an ancillary (β) ion-channel subunit with an important role in fine-tuning cellular excitability. METHODS. We analyzed available single-cell transcriptome data from tens of thousands of murine retinal cells for cell-type-specific expression of Kcne2 using state-of-the-art bioinformatics techniques. This evidence at the transcriptome level was complemented with a comprehensive immunohistochemical characterization of mouse retina (C57BL/6, ages 8-12 weeks) employing co-labeling techniques and cell-type-specific antibody markers. We furthermore examined how conserved the Kcne2 localization pattern in the retina was across species by performing immunostaining on zebrafish, cowbird, sheep, mice, and macaque. RESULTS. Kcne2 is distinctly expressed in cone photoreceptors and rod bipolar cells. At a subcellular level, the bulk of Kcne2 immunoreactivity can be observed in the outer plexiform layer. Here, it localizes into cone pedicles and likely the postsynaptic membrane of the rod bipolar cells. Thus, the vast majority of Kcne2 immunoreactivity is observed in a thin band in the outer plexiform layer. In addition to this, faint Kcne2 immunoreactivity can also be observed in cone inner segments and the somata of a small subset of cone ON bipolar cells. Strikingly, the localization of Kcne2 in the outer plexiform layer was preserved among all of the species studied, spanning at least 300 million years of evolution of the vertebrate kingdom. CONCLUSIONS. The data we present here suggest an important and specific role for Kcne2 in the highly specialized photoreceptor-bipolar cell synapse.

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“…Finally, we used PTESFinder to identify circRNAs present within the RNAseq data of Woods et al (2018), derived from postnatal mouse retina, and compared them with those reported here. Of 25,971 circRNAs identified in mouse, 7358 (∼28.3%) overlap with human retinal circRNAs, and 2414 (∼9.3%) are fully conserved with respect to splice junction use ().…”

Section: Resultsmentioning

confidence: 99%

An integrated transcriptional analysis of the developing human retina

et al. 2019

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The scarcity of embryonic/foetal material as a resource for direct study means that there is still limited understanding of human retina development. Here, we present an integrated transcriptome analysis combined with immunohistochemistry in human eye and retinal samples from 4 to 19 post-conception weeks. This analysis reveals three developmental windows with specific gene expression patterns that informed the sequential emergence of retinal cell types and enabled identification of stage-specific cellular and biological processes, and transcriptional regulators. Each stage is characterised by a specific set of alternatively spliced transcripts that code for proteins involved in the formation of the photoreceptor connecting cilium, pre-mRNA splicing and epigenetic modifiers. Importantly, our data show that the transition from foetal to adult retina is characterised by a large increase in the percentage of mutually exclusive exons that code for proteins involved in photoreceptor maintenance. The circular RNA population is also defined and shown to increase during retinal development. Collectively, these data increase our understanding of human retinal development and the pre-mRNA splicing process, and help to identify new candidate disease genes.

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A comparative analysis of rod bipolar cell transcriptomes identifies novel genes implicated in night vision

Cited by 14 publications

References 58 publications

LRRTM4 is a member of the transsynaptic complex between rod photoreceptors and bipolar cells

LRRTM4 is a member of the transsynaptic complex between rod photoreceptors and bipolar cells

Expression and Localization ofKcne2in the Vertebrate Retina

An integrated transcriptional analysis of the developing human retina

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