<i>Drosophila</i> Atg16 promotes enteroendocrine cell differentiation via regulation of intestinal Slit/Robo signaling

Nagy, Péter; Szatmári, Zsuzsanna; Sándor, Gyöngyvér Orsolya; Lippai, Mónika; Hegedüs, Katalin; Juhász, Gábor

doi:10.1242/dev.147033

Cited by 26 publications

(27 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Interestingly, L. dispar autophagy-related protein 16 (Atg16; Atg16L1 in mammals) was one of 11 DEGs up-regulated after VSV infection that was not up-regulated after VACV coinfection (Dataset S6). Autophagy is a conserved cellular process in which cytosolic components are degraded after targeting to lipid-enclosed vesicles termed "autophagosomes" (63)(64)(65). Fusion of autophagosomes with lysosomes results in the degradation of the membrane-enclosed material and this process requires Atg16 (64).…”

Section: Resultsmentioning

confidence: 99%

“…Autophagy is a conserved cellular process in which cytosolic components are degraded after targeting to lipid-enclosed vesicles termed "autophagosomes" (63)(64)(65). Fusion of autophagosomes with lysosomes results in the degradation of the membrane-enclosed material and this process requires Atg16 (64). Studies in Drosophila have shown that VSV infection induces autophagosome formation and that autophagy contributes to the restriction of VSV (66).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Gypsy moth genome provides insights into flight capability and virus–host interactions

Zhang

Cong

Rex

et al. 2019

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

View full text Add to dashboard Cite

Since its accidental introduction to Massachusetts in the late 1800s, the European gypsy moth (EGM; Lymantria dispar dispar) has become a major defoliator in North American forests. However, in part because females are flightless, the spread of the EGM across the United States and Canada has been relatively slow over the past 150 years. In contrast, females of the Asian gypsy moth (AGM; Lymantria dispar asiatica) subspecies have fully developed wings and can fly, thereby posing a serious economic threat if populations are established in North America. To explore the genetic determinants of these phenotypic differences, we sequenced and annotated a draft genome of L. dispar and used it to identify genetic variation between EGM and AGM populations. The 865-Mb gypsy moth genome is the largest Lepidoptera genome sequenced to date and encodes ∼13,300 proteins. Gene ontology analyses of EGM and AGM samples revealed divergence between these populations in genes enriched for several gene ontology categories related to muscle adaptation, chemosensory communication, detoxification of food plant foliage, and immunity. These genetic differences likely contribute to variations in flight ability, chemical sensing, and pathogen interactions among EGM and AGM populations. Finally, we use our new genomic and transcriptomic tools to provide insights into genome-wide gene-expression changes of the gypsy moth after viral infection. Characterizing the immunological response of gypsy moths to virus infection may aid in the improvement of virus-based bioinsecticides currently used to control larval populations.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Gypsy moth genome provides insights into flight capability and virus–host interactions

Zhang

Cong

Rex

et al. 2019

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

View full text Add to dashboard Cite

show abstract

“…In Drosophila, ATG16 is crucial for the differentiation of intestinal stem cells into enteroendocrine (EE) cells. Expression of ATG16 lacking the WD40 repeat domain led to morphological changes in the intestine that resembled inflammatory bowel disease (Nagy et al, 2017). Furthermore, the C-terminal WD40 domain is important in xenophagy (Xiong et al, 2019).…”

Section: Further Autophagy-independent Functions Of Atg5 Atg12 and Amentioning

confidence: 99%

Dictyostelium discoideum and autophagy – a perfect pair

Fischer¹,

Eichinger²

2019

Int. J. Dev. Biol.

View full text Add to dashboard Cite

Autophagy is subdivided into chaperone-mediated autophagy, microautophagy and macroautophagy and is a highly conserved intracellular degradative pathway. It is crucial for cellular homeostasis and also serves as a response to different stresses. Here we focus on macroautophagy, which targets damaged organelles and large protein assemblies, as well as pathogenic intracellular microbes for destruction. During this process, cytosolic material becomes enclosed in newly generated double-membrane vesicles, the so-called autophagosomes. Upon maturation, the autophagosome fuses with the lysosome for degradation of the cargo. The basic molecular machinery that controls macroautophagy works in a sequential order and consists of the ATG1 complex, the PtdIns3K complex, the membrane delivery system, two ubiquitin-like conjugation systems, and autophagy adaptors and receptors. Since the different stages of macroautophagy from initiation to final degradation of cargo are tightly regulated and highly conserved across eukaryotes, simple model organisms in combination with a wide range of techniques contributed significantly to advance our understanding of this complex dynamic process. Here, we present the social amoeba Dictyostelium discoideum as an advantageous and relevant experimental model system for the analysis of macroautophagy.KEY WORDS: autophagy, ubiquitin-proteasome system (UPS), LC3-associated phagocytosis, proteaphagy Int. J. Dev. Biol. 63: 485-495 (2019)

show abstract

“…For instance, autophagy‐related gene FIP200 plays a vital role in the maintenance and differentiation of postnatal neural stem cells, and its deletion leads to accumulation of p62 in order to regulate the cell fate through activation of superoxide . Another gene, Atg16, plays a critical role in gut homeostasis and its mutation causes an impaired Slit/Robo‐dependent differentiation of the enteroendocrine cells to trigger inflammation, which may increase the risk of developing colorectal cancer . The autophagy factor UVRAG, present in the Beclin1/Vps34 complex, is mutated in several cancers, causing an abnormal left‐right axis formation, leading to heterotaxy .…”

Section: Introductionmentioning

confidence: 99%

“…15 Another gene, Atg16, plays a critical role in gut homeostasis and its mutation causes an impaired Slit/Robodependent differentiation of the enteroendocrine cells to trigger inflammation, which may increase the risk of developing colorectal cancer. 16 The autophagy factor UVRAG, present in the Beclin1/Vps34 complex, is mutated in several cancers, causing an abnormal left-right axis formation, leading to heterotaxy. 17 Furthermore, depletion of Beclin1 has been reported to inhibit both autophagy and differentiation capabilities.…”

mentioning

confidence: 99%

Abrus agglutinin stimulates BMP‐2‐dependent differentiation through autophagic degradation of β‐catenin in colon cancer stem cells

Panda

Naik

Praharaj

et al. 2018

Molecular Carcinogenesis

View full text Add to dashboard Cite

Eradicating cancer stem cells (CSCs) in colorectal cancer (CRC) through differentiation therapy is a promising approach for cancer treatment. Our retrospective tumor-specimen analysis elucidated alteration in the expression of bone morphogenetic protein 2 (BMP-2) and β-catenin during the colon cancer progression, indicating that their possible intervention through "forced differentiation" in colon cancer remission. We reveal that Abrus agglutinin (AGG) induces the colon CSCs differentiation, and enhances sensitivity to the anticancer therapeutics. The low dose AGG (max. dose = 100 ng/mL) decreased the expression of stemness-associated molecules such as CD44 and β-catenin in the HT-29 cell derived colonospheres. Further, AGG augmented colonosphere differentiation, as demonstrated by the enhanced CK20/CK7 expression ratio and induced alkaline phosphatase activity. Interestingly, the AGG-induced expression of BMP-2 and the AGG-induced differentiation were demonstrated to be critically dependent on BMP-2 in the colonospheres. Similarly, autophagy-induction by AGG was associated with colonosphere differentiation and the gene silencing of BMP-2 led to the reduced accumulation of LC3-II, suggesting that AGG-induced autophagy is dependent on BMP-2. Furthermore, hVps34 binds strongly to BMP-2, indicating a possible association of BMP-2 with the process of autophagy. Moreover, the reduction in the self-renewal capacity of the colonospheres was associated with AGG-augmented autophagic degradation of β-catenin through an interaction with the autophagy adaptor protein p62. In the subcutaneous HT-29 xenograft model, AGG profoundly inhibited the growth of tumors through an increase in BMP-2 expression and LC3-II puncta, and a decrease in β-catenin expression, confirming the antitumor potential of AGG through induction of differentiation in colorectal cancer.

show abstract

Drosophila Atg16 promotes enteroendocrine cell differentiation via regulation of intestinal Slit/Robo signaling

Cited by 26 publications

References 61 publications

Gypsy moth genome provides insights into flight capability and virus–host interactions

Gypsy moth genome provides insights into flight capability and virus–host interactions

Dictyostelium discoideum and autophagy – a perfect pair

Abrus agglutinin stimulates BMP‐2‐dependent differentiation through autophagic degradation of β‐catenin in colon cancer stem cells

Contact Info

Product

Resources

About