Calcium-Induced Conformational Transition of Trout Ependymins Monitored by Tryptophan Fluorescence

Ganß, Bernhard; Hoffmann, Werner

doi:10.2174/1874091x00903010014

Cited by 17 publications

(10 citation statements)

References 36 publications

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“…Therefore, EPDRs may act as ligands themselves, in addition to being able to bind other ligands within their central pocket. Additional biochemical properties found for fish ependymins are also likely to be important for EPDR function, including the ability to form disulphide-bound dimers [ 44 ] and higher molecular weight aggregates [ 45 , 46 ], the presence of N-linked carbohydrates that confer Ca 2 + or cell-cell/cell-matrix binding ability [ 2 , 3 ], and the ability to change structural conformation in the presence of Ca 2 + [ 47 ]. Discovering whether these properties are associated with the conserved cysteine residues characteristic of the EPDRs, and how they relate to each of the three conserved profiles identified here, will be an interesting avenue of future research.…”

Section: Discussionmentioning

confidence: 99%

The evolution of ependymin-related proteins

et al. 2018

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BackgroundEpendymins were originally defined as fish-specific secreted glycoproteins involved in central nervous system plasticity and memory formation. Subsequent research revealed that these proteins represent a fish-specific lineage of a larger ependymin-related protein family (EPDRs). EPDRs have now been identified in a number of bilaterian animals and have been implicated in diverse non-neural functions. The recent discoveries of putative EPDRs in unicellular holozoans and an expanded EPDR family with potential roles in conspecific communication in crown-of-thorns starfish suggest that the distribution and diversity of EPDRs is significantly broader than currently understood.ResultsWe undertook a systematic survey to determine the distribution and evolution of EPDRs in eukaryotes. In addition to Bilateria, EPDR genes were identified in Cnidaria, Placozoa, Porifera, Choanoflagellatea, Filasterea, Apusozoa, Amoebozoa, Charophyta and Percolozoa, and tentatively in Cercozoa and the orphan group Malawimonadidae. EPDRs appear to be absent from prokaryotes and many eukaryote groups including ecdysozoans, fungi, stramenopiles, alveolates, haptistans and cryptistans. The EPDR family can be divided into two major clades and has undergone lineage-specific expansions in a number of metazoan lineages, including in poriferans, molluscs and cephalochordates. Variation in a core set of conserved residues in EPDRs reveals the presence of three distinct protein types; however, 3D modelling predicts overall protein structures to be similar.ConclusionsOur results reveal an early eukaryotic origin of the EPDR gene family and a dynamic pattern of gene duplication and gene loss in animals. This research provides a phylogenetic framework for the analysis of the functional evolution of this gene family.Electronic supplementary materialThe online version of this article (10.1186/s12862-018-1306-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

The evolution of ependymin-related proteins

et al. 2018

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“…The dissemination of cancer cells may be facilitated by the effects of EPDR1 on adhesion to type I collagen fibres, which have been described as the "highways" for tumour cell migration 31 . The interaction of fish ependymins with collagen is calcium-dependent 13 ; should this dependence also take place in EPDR1, an interesting consequence might result. STIM1 has been found to be overexpressed in CRC and promotes cell motility and EMT 34,35 .…”

Section: Discussionmentioning

confidence: 99%

EPDR1 up-regulation in human colorectal cancer is related to staging and favours cell proliferation and invasiveness

Gimeno-Valiente

Riffo‐Campos

Ayala

et al. 2020

Sci Rep

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The finding of novel molecular markers for prediction or prognosis of invasiveness in colorectal cancer (cRc) constitutes an appealing challenge. Here we show the up-regulation of EPDR1 in a prospective cohort of 101 CRC patients, in a cDNA array of 43 patients and in in silico analyses. EPDR1 encodes a protein related to ependymins, a family of glycoproteins involved in intercellular contacts. A thorough statistical model allowed us to conclude that the gene is significantly up-regulated in tumour tissues when compared with normal mucosa. these results agree with those obtained by the analysis of three publicly available databases. EPDR1 up-regulation correlates with the tnM staging parameters, especially t and M. Studies with cRc cell lines revealed that the methylation of a cpG island controls EPDR1 expression. siRNA knocking-down and overexpression of the gene following transient plasmid transfection, showed that EPDR1 favours cell proliferation, migration, invasiveness and adhesion to type I collagen fibres, suggesting a role in epithelial to mesenchymal transition. Both statistical and functional analysis correlated EPDR1 overexpression with invasiveness and dissemination of tumour cells, supporting the inclusion of EPDR1 in panels of genes used to improve molecular subtyping of cRc. eventually, EPDR1 may be an actionable target. Colorectal cancer (CRC) is one of the most common malignancies worldwide 1. In spite of the progresses of precision medicine, the long-term survival of patients with advanced metastatic disease is still poor 2 and the burden of CRC is expected to increase by 60% in the next decade 1. Nevertheless, this disease is a good candidate for screening programmes 3 and its early detection improve treatment and survival. Most of CRC-related death is due to tumour metastasis 4 and, therefore, finding of molecular markers for prediction or prognosis of invasiveness, which could be added to the available repertoire of potential markers 5-7 , constitutes an appealing challenge. This is particularly attractive in view of the growing interest in improving the clinical stratification of CRC 8,9. This reason, together with the risks of metastatic dissemination, makes especially interesting the identification of potential actionable targets in CRC. The EPDR1 gene codes for a protein related to ependymins, a family of piscine brain glycoproteins 10. Ependymins, encoded by Epd genes, are transmembrane proteins that play a role in intercellular contacts between neural cells 11. It was early suggested that their extracellular domain may display antiadhesive properties 12 and it shows a calcium-dependent ability to interact with collagen fibrils 13 .

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“…Although expressed in many tissues and with little amino acid similarity, all ependymin-related proteins are secretory, calcium-binding glycoproteins that can undergo conformational changes and associate with collagen in the ECM. They have been involved in regeneration, nerve growth, cell contact, adhesion and migration processes [90]. We hypothesize that ependymin-related proteins, and potentially some of the other ECM proteins highly expressed in triphasic individuals, are part of the “fibrillar substance” that lies between the stalk and the electrocyte body in individuals with penetrating electrocytes [50].…”

Section: Discussionmentioning

confidence: 99%

The transcriptional correlates of divergent electric organ discharges inParamormyropselectric fish

Losilla

Gallant

2019

Preprint

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12Background: Understanding the genomic basis of phenotypic diversity can be greatly facilitated 13 by examining adaptive radiations with hypervariable traits. In this study, we focus on a rapidly 14 diverged species group of mormyrid electric fish in the genus Paramormyrops, which are 15 characterized by extensive phenotypic variation in electric organ discharges (EODs). The main 16 components of EOD diversity are waveform duration, complexity and polarity. Using an RNA-17 sequencing based approach, we sought to identify gene expression correlates for each of these 18 EOD waveform features by comparing 11 specimens of Paramormyrops that exhibit variation in 19 these features. 20Results: Patterns of gene expression among Paramormyrops are highly correlated, and 3,274 21 genes (16%) were differentially expressed. Using our most restrictive criteria, we detected 71-22 144 differentially expressed genes correlated with each EOD feature, with little overlap between 23 them. The predicted functions of several of these genes are related to extracellular matrix, cation 24 homeostasis, lipid metabolism, and cytoskeletal and sarcomeric proteins. These genes are of 25 significant interest given the known morphological differences between electric organs that 26 underlie differences in the EOD waveform features studied. 27Conclusions: In this study, we identified plausible candidate genes that may contribute to 28 phenotypic differences in EOD waveforms among a rapidly diverged group of mormyrid electric 29 fish. These genes may be important targets of selection in the evolution of species-specific 30 differences in mate-recognition signals.Understanding the genomic basis of phenotypic diversity is a major goal of evolutionary 33 biology [1]. Adaptive radiations and explosive diversification of species [2] are frequently 34 characterized by interspecific phenotypic differences in divergence of few, hypervariable 35 phenotypic traits [3][4][5][6]. Such systems offer exceptional advantages to study the genomic bases of 36 phenotypic diversity: they can provide replication under a controlled phylogenetic framework 37 [7], and couple ample phenotypic differentiation with relatively "clean" genomic signals between 38 recently diverged species [8]. Study of the genomic mechanisms underlying hypervariable 39 phenotypic traits has identified, in some cases relatively simple genetic architectures [9][10][11][12][13]. 40 More often, the genetic architecture underlying such traits can be complex and polygenic [14-41 17]. It has long been recognized that changes in gene expression can affect phenotypic 42 differences between species [18], and RNA-seq based approaches have greatly facilitated the 43 study of this relationship [19]. A growing number of studies have examined differences in gene 44 expression in phenotypic evolution (e.g., [19][20][21][22][23][24][25][26][27]). While these studies do not implicate 45 mutational causes, analysis of differential gene expression (DGE) can be a useful approach in 46 examining the ...

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Calcium-Induced Conformational Transition of Trout Ependymins Monitored by Tryptophan Fluorescence

Cited by 17 publications

References 36 publications

The evolution of ependymin-related proteins

The evolution of ependymin-related proteins

EPDR1 up-regulation in human colorectal cancer is related to staging and favours cell proliferation and invasiveness

The transcriptional correlates of divergent electric organ discharges inParamormyropselectric fish

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