scholarly journals Neuroglian regulates Drosophila intestinal stem cell proliferation through enhanced signaling via the Epidermal Growth Factor Receptor

2020 ◽  
Author(s):  
Martin Resnik-Docampo ◽  
Kathleen M. Cunningham ◽  
S. Mateo Ruvalcaba ◽  
Charles Choi ◽  
Vivien Sauer ◽  
...  
Keyword(s):  
Stem Cell ◽  
Null Allele ◽  
Growth Factor Receptor ◽  
Septate Junction ◽  
Intestinal Stem Cells ◽  
Cell Behavior ◽  
Egfr Activation ◽  
Genetic Epistasis ◽  
Epidermal Growth

SummaryThe Drosophila melanogaster intestine is an excellent system for elucidating mechanisms regulating stem cell behavior under homeostatic conditions or in response to injury, stress, or ageing. Here we show that the septate junction (SJ) protein Neuroglian (Nrg) is expressed in intestinal stem cells (ISCs) and daughter enteroblasts (EBs) within the fly midgut, the equivalent of the mammalian small intestine. Although Nrg localizes to the plasma membrane, SJs are not present between ISC/EBs, suggesting Nrg plays a different role in this tissue. Generation of ISCs homozygous for a null allele of Nrg revealed that Nrg is required for ISC proliferation in young flies, and depletion of Nrg from ISCs/EBs was able to suppress the increase in ISC proliferation with age. Conversely, overexpression of Nrg in ISC/EBs was sufficient to drive ISC proliferation, leading to an increase in cells expressing ISC/EB markers. In addition, we observed an increase in EGFR activation. Genetic epistasis experiments revealed that Nrg acts upstream of EGFR in the midgut to regulate ISC proliferation. As Nrg function is highly conserved in mammalian systems, our work characterizing the role of Nrg in the intestine has implications for the etiology and treatment of intestinal disorders due to altered ISC behavior.

The regulatory role of the juxtamembrane region in the activity of the epidermal growth factor receptor

2012 ◽  
Vol 40 (1) ◽  
pp. 195-199 ◽  
Author(s):  
Aislyn D.W. Boran
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Structural Data ◽  
Juxtamembrane Region ◽  
Egfr Activation ◽  
Epidermal Growth ◽  
The Subject

Although the EGFR (epidermal growth factor receptor) was discovered over 30 years ago, its mechanism of activation is still the subject of intense study. There are many published studies on the mechanism of EGFR activation and regulation, including biochemical and biophysical analyses and crystallographic structures of EGFR in different activation states and conformations, mutated at various amino acids or bound to different pharmacological inhibitors. The cumulative biochemical, biophysical and structural data have led to a nearly complete account of the mechanism of activation of EGFR. The role of the JXM (juxtamembrane) domain in EGFR structure and activity has only recently begun to be elucidated through biochemical, biophysical and structural studies. In the present article, I review the studies that have highlighted the role of the JXM domain in EGFR activation.

scholarly journals Porcine Epidemic Diarrhea Virus-Induced Epidermal Growth Factor Receptor Activation Impairs the Antiviral Activity of Type I Interferon

2018 ◽  
Vol 92 (8) ◽  
Author(s):  
Lijun Yang ◽  
Jiayu Xu ◽  
Longjun Guo ◽  
Taijie Guo ◽  
Lu Zhang ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Type I Interferon ◽  
Growth Factor Receptor ◽  
Type I ◽  
Specific Inhibition ◽  
Diarrhea Virus ◽  
Egfr Activation ◽  
Epidermal Growth ◽  
Porcine Epidemic Diarrhea

ABSTRACTPorcine epidemic diarrhea virus (PEDV) causes acute and devastating enteric disease in suckling piglets and results in huge economic losses in the pig industry worldwide. To establish productive infection, viruses must first circumvent the host innate immune response. In this study, we found that PEDV infection stimulated epidermal growth factor receptor (EGFR) activation, which has been linked to not only anticancer therapeutics, but also antiviral signaling. Therefore, we determined whether EGFR activation affected PEDV infection by using an activator or overexpression assay. The data showed that EGFR activation enhanced virus replication in both cases. We also found that specific inhibition of EGFR by either inhibitors or small interfering RNA (siRNA) led to a decrease in virus yields. Further analysis revealed that inhibition of EGFR produced augmentation of type I interferon genes. We next observed that the EGFR downstream cascade STAT3 was also activated upon PEDV infection. Similar to the case of EGFR, specific inhibition of STAT3 by either inhibitor or siRNA increased the antiviral activity of interferon and resulted in decreased PEDV RNA levels, and vice versa. The data on STAT3 depletion in combination with EGFR activation suggest that the attenuation of antiviral activity by EGFR activation requires activation of the STAT3 signaling pathway. Taken together, these data demonstrate that PEDV-induced EGFR activation serves as a negative regulator of the type I interferon response and provides a novel therapeutic target for virus infection.IMPORTANCEEGFR is a transmembrane tyrosine receptor that mediates various cellular events, as well as several types of human cancers. In this study, we investigated for the first time the role of EGFR in PEDV infection. We observed that PEDV infection induced EGFR activation. The role of EGFR activation is to impair the antiviral activity of type I interferon, which requires the involvement of the EGFR downstream signaling cascade STAT3. Our findings reveal a new mechanism evolved by PEDV to circumvent the host antiviral response, which might serve as a therapeutic target against virus infection.

scholarly journals Role of epidermal growth factor receptor degradation in gemcitabine-mediated cytotoxicity

Oncogene ◽  
2006 ◽  
Vol 26 (23) ◽  
pp. 3431-3439 ◽  
Author(s):  
F Y Feng ◽  
S Varambally ◽  
S A Tomlins ◽  
P Y Chun ◽  
C A Lopez ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Epidermal Growth

scholarly journals CG6015 controls spermatogonia transit-amplifying divisions by epidermal growth factor receptor signaling in Drosophila testes

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Jun Yu ◽  
Qianwen Zheng ◽  
Zhiran Li ◽  
Yunhao Wu ◽  
Yangbo Fu ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Stem Cell ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Gene Set Enrichment Analysis ◽  
Germline Stem Cell ◽  
Egfr Signaling ◽  
Egfr Signaling Pathway ◽  
Epidermal Growth

AbstractSpermatogonia transit-amplifying (TA) divisions are crucial for the differentiation of germline stem cell daughters. However, the underlying mechanism is largely unknown. In the present study, we demonstrated that CG6015 was essential for spermatogonia TA-divisions and elongated spermatozoon development in Drosophila melanogaster. Spermatogonia deficient in CG6015 inhibited germline differentiation leading to the accumulation of undifferentiated cell populations. Transcriptome profiling using RNA sequencing indicated that CG6015 was involved in spermatogenesis, spermatid differentiation, and metabolic processes. Gene Set Enrichment Analysis (GSEA) revealed the relationship between CG6015 and the epidermal growth factor receptor (EGFR) signaling pathway. Unexpectedly, we discovered that phosphorylated extracellular regulated kinase (dpERK) signals were activated in germline stem cell (GSC)-like cells after reduction of CG6015 in spermatogonia. Moreover, Downstream of raf1 (Dsor1), a key downstream target of EGFR, mimicked the phenotype of CG6015, and germline dpERK signals were activated in spermatogonia of Dsor1 RNAi testes. Together, these findings revealed a potential regulatory mechanism of CG6015 via EGFR signaling during spermatogonia TA-divisions in Drosophila testes.

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