A novel gene encoding a putative transmembrane protein with two extracellular CUB domains and a low-density lipoprotein class A module: isolation of alternatively spliced isoforms in retina and brain

Stöhr, Heidi; Berger, C; Fröhlich, Susanne; Weber, Bernhard H. F.

doi:10.1016/s0378-1119(02)00438-9

Cited by 60 publications

(60 citation statements)

References 29 publications

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“…Moreover, specific expression in the brain and retina was expected for both of the NETO family genes [3,7,13]. The two genes are poorly understood; it was not until 2002 that they come to be studied [3].…”

Section: Discussionmentioning

confidence: 99%

“…The results identified the NETO2 gene as a new potential molecular marker of renal cell can cer. The gene codes for a membrane protein, which is poorly understood and, along with its only paralog NETO1, belongs to the unique subfamily of CUB and LDLa containing proteins [3]. The NETO1 and NETO2 proteins were found to play a role in neuron specific processes, in particular, the formation of a regulatory complex with kainate type receptors [4].…”

Section: Introductionmentioning

confidence: 99%

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Increase in NETO2 gene expression is a potential molecular genetic marker in renal and lung cancers

et al. 2012

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Multiple changes in the genome, transcriptome, and proteome are frequent in cancer cells. A search for molecular markers based on DNA, mRNA, or proteins is a main method to develop early specific diagnostics for cancer. While universal markers are still unavailable, similar trends are known for the expres sion patterns of particular genes in certain epithelial tumors. A bioinformatic screening of transcriptomic databases identified the NETO2 gene as a new potential promising marker of renal cancer. A substantial increase in NETO2 mRNA level was detected in 90% clear cell renal cell carcinomas, 70% of non small cell lung cancers, and 50% of papillary renal cancers by real time PCR. The NETO2 mRNA level was increased to a lesser extent in cervical carcinoma and colon cancer and tended to decrease in cancer of the stomach. The NETO2 gene, which codes for a membrane glycoprotein with an unclear function, was assumed to pro vide a new promising marker for early diagnosis in renal cancer and non small cell lung cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Increase in NETO2 gene expression is a potential molecular genetic marker in renal and lung cancers

et al. 2012

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“…Other SOL-1-like molecules that contribute to iGluR function have not been identified; however, LEV-10 (a CUB-domain single-pass transmembrane protein) was identified in C. elegans and is required for the clustering and, possibly, function of a subclass of acetylcholine receptors (19). There are many predicted CUB domain proteins in vertebrate nervous systems, including NETO1 and NETO2, which are highly expressed in retina and brain (20,21). Because many proteins that are required for synaptic function are evolutionarily conserved, it is possible that CUB domain proteins will be discovered in vertebrates that also have unanticipated roles at the synapse.…”

Section: Discussionmentioning

confidence: 99%

SOL-1 is an auxiliary subunit that modulates the gating of GLR-1 glutamate receptors in Caenorhabditis elegans

Zheng

Brockie

Mellem

et al. 2006

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

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Most rapid excitatory synaptic signaling in the brain is mediated by postsynaptic ionotropic glutamate receptors (iGluRs) that are gated open by the neurotransmitter glutamate. In Caenorhabditis elegans, sol-1 encodes a CUB-domain transmembrane protein that is required for currents that are mediated by the GLR-1 iGluR. Mutations in sol-1 do not affect GLR-1 expression, localization, membrane insertion, or stabilization at synapses, suggesting that SOL-1 is required for iGluR function. Here, we provide evidence that SOL-1 is an auxiliary subunit that modulates the gating of GLR-1 receptors. We show that mutant variants of GLR-1 with altered gating partially restore glutamate-gated current and GLR-1-dependent behaviors in sol-1 mutants. Domain analysis of SOL-1 indicates that extracellular CUB domain 3 is required for function and that a secreted variant partially restores glutamate-gated currents and behavior. Also, we show that endogenous glutamatergic synaptic currents are absent in sol-1 mutants. Our data suggest that GLR-1 iGluRs are not simply stand-alone molecules and require the SOL-1 auxiliary protein to promote the open state of the receptor. Our analysis presents the possibility that glutamatergic signaling in other organisms may be similarly modified by SOL-1-like transmembrane proteins. Most fast synaptic neurotransmission in the vertebrate central nervous system is mediated by ionotropic glutamate receptors (iGluRs) that are gated by the neurotransmitter glutamate. The non-NMDA class of iGluRs are gated by the ligand ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or kainate (1). Recently, SOL-1 was shown to be specifically required for non-NMDA-type glutamate-gated currents mediated by the Caenorhabditis elegans iGluR GLR-1 (2). Transgenic worms that express the gain-of-function GLR-1(A687T) (referred to as the lurcher variant) have forward movements that are much briefer than WT, causing a ''lurching'' phenotype (2, 3). In sol-1 mutants, the lurching behavior is suppressed, and kainate-gated currents are absent. In contrast, NMDA-dependent currents (4), are not disrupted in sol-1 mutants. How SOL-1 contributes to glutamate-gated currents is not well understood. SOL-1 and GLR-1 colocalize at puncta in ventral cord processes that are presumed to be points of synaptic contact. Furthermore, coimmunoprecipitation experiments indicate that SOL-1 and GLR-1 form a complex in COS-7 cells (2). These data suggest that SOL-1 may function as a GLR-1 auxiliary subunit.In sol-1 mutants, GLR-1 is expressed on the cell surface, but the mutants have a phenotype that is consistent with disrupted glutamatergic neurotransmission. Furthermore, no kainate-gated currents can be recorded from the AVA interneurons, suggesting that SOL-1 could modify ligand-binding or receptor gating, which is defined broadly here to include the transitions between closed, open, and desensitized states. We have addressed these possibilities by using two genetic strategies. First, we generated a series of truncated versions of SOL...

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“…Three alternatively spliced variants are generated through alternate usage of two leader exons (1a and 1b) and exon 5 (Stohr et al, 2002). The soluble isoform 1 which contains only one CUB domain is restricted to the retina.…”

Section: Neto1mentioning

confidence: 99%

Evolutionary conservation of alternative splicing in chicken

Katyal¹,

Gao²,

Liu³

et al. 2007

Cytogenet Genome Res

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Alternative splicing represents a source of great diversity for regulating protein expression and function. It has been estimated that one-third to two-thirds of mammalian genes are alternatively spliced. With the sequencing of the chicken genome and analysis of transcripts expressed in chicken tissues, we are now in a position to address evolutionary conservation of alternative splicing events in chicken and mammals. Here, we compare chicken and mammalian transcript sequences of 41 alternatively-spliced genes and 50 frequently accessed genes. Our results support a high frequency of splicing events in chicken, similar to that observed in mammals.

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A novel gene encoding a putative transmembrane protein with two extracellular CUB domains and a low-density lipoprotein class A module: isolation of alternatively spliced isoforms in retina and brain

Cited by 60 publications

References 29 publications

Increase in NETO2 gene expression is a potential molecular genetic marker in renal and lung cancers

Increase in NETO2 gene expression is a potential molecular genetic marker in renal and lung cancers

SOL-1 is an auxiliary subunit that modulates the gating of GLR-1 glutamate receptors in Caenorhabditis elegans

Evolutionary conservation of alternative splicing in chicken

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