Involvement of CD9 and PDGFR in migration is evolutionarily conserved from Drosophila glia to human glioma

Jeibmann, Astrid; Halama, Kathrin; Witte, Hanna Theresa; Kim, Su Na; Eikmeier, Kristin; Koos, Björn; Klämbt, Christian; Paulus, Werner

doi:10.1007/s11060-015-1864-4

Cited by 13 publications

(6 citation statements)

References 37 publications

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“…Upregulation or de novo expression of PDGF-BB has been described in mesangial cells, podocyte vascular cells, tubular and interstitial cells in animal models, and human renal diseases in many studies 55 . The PDGFR has also been reported to associate with CD9 10 , and PDGFRβ levels and activation were indeed reduced upon CD9 depletion. Potentiation of EGFR and PDGFR pathways would be predicted to enable chemotaxis by increasing engagement of downstream effectors, such as FAK.…”

Section: Discussionmentioning

confidence: 95%

“…Due to its specific structure, CD9 has the ability to interact with several partners. CD9 has been described to associate with CD44 and the pre-β1 integrin subunit 6,7 , the growth factor heparin-binding EGF-like growth factor (HB-EGF) 8 , as well as with epidermal growth factor receptor (EGFR) 9 and platelet-derived growth factor receptor (PDGFR) 10 . HB-EGF-dependent EGFR activation and PDGF triggering have been previously implicated in CGN and membranoproliferative glomerulonephritis 11–15 , although it is unknown if they modulate the PEC phenotype.…”

Section: Introductionmentioning

confidence: 99%

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The tetraspanin CD9 controls migration and proliferation of parietal epithelial cells and glomerular disease progression

et al. 2019

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The mechanisms driving the development of extracapillary lesions in focal segmental glomerulosclerosis (FSGS) and crescentic glomerulonephritis (CGN) remain poorly understood. A key question is how parietal epithelial cells (PECs) invade glomerular capillaries, thereby promoting injury and kidney failure. Here we show that expression of the tetraspanin CD9 increases markedly in PECs in mouse models of CGN and FSGS, and in kidneys from individuals diagnosed with these diseases. Cd9 gene targeting in PECs prevents glomerular damage in CGN and FSGS mouse models. Mechanistically, CD9 deficiency prevents the oriented migration of PECs into the glomerular tuft and their acquisition of CD44 and β1 integrin expression. These findings highlight a critical role for de novo expression of CD9 as a common pathogenic switch driving the PEC phenotype in CGN and FSGS, while offering a potential therapeutic avenue to treat these conditions.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

The tetraspanin CD9 controls migration and proliferation of parietal epithelial cells and glomerular disease progression

et al. 2019

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“…demonstrated that HCMV entry into lung fibroblasts and glioma cells depends on PDGFR-α and results in the phosphorylation of the receptor [ 80 , 83 ]. CD9 is known to associate with PDGFR-α [ 84 ] and tetraspanins residing in TEMs haven been shown to influence signaling of many receptor tyrosine kinases (reviewed in [ 85 ]). It is possible that TEM-mediated enhancement of receptor tyrosine kinase signaling is important for HCMV entry.…”

Section: Discussionmentioning

confidence: 99%

Quantitative membrane proteomics reveals a role for tetraspanin enriched microdomains during entry of human cytomegalovirus

et al. 2017

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Human cytomegalovirus (HCMV) depends on and modulates multiple host cell membrane proteins during each stage of the viral life cycle. To gain a global view of the impact of HCMV-infection on membrane proteins, we analyzed HCMV-induced changes in the abundance of membrane proteins in fibroblasts using stable isotope labeling with amino acids (SILAC), membrane fractionation and protein identification by two-dimensional liquid chromatography and tandem mass spectrometry. This systematic approach revealed that CD81, CD44, CD98, caveolin-1 and catenin delta-1 were down-regulated during infection whereas GRP-78 was up-regulated. Since CD81 downregulation was also observed during infection with UV-inactivated virus we hypothesized that this tetraspanin is part of the viral entry process. Interestingly, additional members of the tetraspanin family, CD9 and CD151, were also downregulated during HCMV-entry. Since tetraspanin-enriched microdomains (TEM) cluster host cell membrane proteins including known CMV receptors such as integrins, we studied whether TEMs are required for viral entry. When TEMs were disrupted with the cholesterol chelator methyl-β-cylcodextrin, viral entry was inhibited and this inhibition correlated with reduced surface levels of CD81, CD9 and CD151, whereas integrin levels remained unchanged. Furthermore, simultaneous siRNA-mediated knockdown of multiple tetraspanins inhibited viral entry whereas individual knockdown had little effect suggesting essential, but redundant roles for individual tetraspanins during entry. Taken together, our data suggest that TEM act as platforms for receptors utilized by HCMV for entry into cells.

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“…In fact, 82% of the protein's sequence was modelled with 100% confidence by the single highest scoring template. In the literature, human tspan29 has been referred as being a close homolog of tsp2a that modulates platelet‐derived growth factor receptor (PDGFR) signalling during gliomagenesis 133 . Tspan8 has also been found to promote tumour progression in glioma 134 and several other types of human cancer as well 135 .…”

Section: Prediction Of Human Orthologs To the Drosophila's Sj‐relatedmentioning

confidence: 99%

The Drosophila septate junctions beyond barrier function: Review of the literature, prediction of human orthologs of the SJ‐related proteins and identification of protein domain families

et al. 2020

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The involvement of Septate Junctions (SJs) in critical cellular functions that extend beyond their role as diffusion barriers in the epithelia and the nervous system has made the fruit fly an ideal model for the study of human diseases associated with impaired Tight Junction (TJ) function. In this study, we summarized current knowledge of the Drosophila melanogaster SJ‐related proteins, focusing on their unconventional functions. Additionally, we sought to identify human orthologs of the corresponding genes as well as protein domain families. The systematic literature search was performed in PubMed and Scopus databases using relevant key terms. Orthologs were predicted using the DIOPT tool and aligned protein regions were determined from the Pfam database. 3‐D models of the smooth SJ proteins were built on the Phyre2 and DMPFold protein structure prediction servers. A total of 30 proteins were identified as relatives to the SJ cellular structure. Key roles of these proteins, mainly in the regulation of morphogenetic events and cellular signalling, were highlighted. The investigation of protein domain families revealed that the SJ‐related proteins contain conserved domains that are required not only for cell‐cell interactions and cell polarity but also for cellular signalling and immunity. DIOPT analysis of orthologs identified novel human genes as putative functional homologs of the fruit fly SJ genes. A gap in our knowledge was identified regarding the domains that occur in the proteins encoded by eight SJ‐associated genes. Future investigation of these domains is needed to provide functional information.

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Involvement of CD9 and PDGFR in migration is evolutionarily conserved from Drosophila glia to human glioma

Cited by 13 publications

References 37 publications

The tetraspanin CD9 controls migration and proliferation of parietal epithelial cells and glomerular disease progression

The tetraspanin CD9 controls migration and proliferation of parietal epithelial cells and glomerular disease progression

Quantitative membrane proteomics reveals a role for tetraspanin enriched microdomains during entry of human cytomegalovirus

The Drosophila septate junctions beyond barrier function: Review of the literature, prediction of human orthologs of the SJ‐related proteins and identification of protein domain families

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