Workflow of PathwayLinker with the <i>C. elegans</i> gene <i>cdc-25.1</i> as an example.

<p>Workflow of PathwayLinker with the <i>C. elegans</i> gene <i>cdc-25.1</i> as an example.</p

Functions of the report page of PathwayLinker.

<p>All nodes (proteins) and edges (interactions) can be clicked for further information. Proteins and interactions can be highlighted by selecting their known signaling pathways and by selecting their known interaction types, respectively. A built-in statistical enrichment test and direct hyperlinks to analyses by external resources are also available. These allow the user to select the most significantly enriched functions within the group of proteins made up of the queried protein(s) and its (their) interactors. The report is available in PDF and plain text (machine readable) formats. The user can have the stable URL of the report e-mailed to a selected address.</p

Developmentally regulated autophagy is required for eye formation in <i>Drosophila</i>

<p>The compound eye of the fruit fly <i>Drosophila melanogaster</i> is one of the most intensively studied and best understood model organs in the field of developmental genetics. Herein we demonstrate that autophagy, an evolutionarily conserved selfdegradation process of eukaryotic cells, is essential for eye development in this organism. Autophagic structures accumulate in a specific pattern in the developing eye disc, predominantly in the morphogenetic furrow (MF) and differentiation zone. Silencing of several autophagy genes (<i>Atg</i>) in the eye primordium severely affects the morphology of the adult eye through triggering ectopic cell death. In <i>Atg</i> mutant genetic backgrounds however genetic compensatory mechanisms largely rescue autophagic activity in, and thereby normal morphogenesis of, this organ. We also show that in the eye disc the expression of a key autophagy gene, <i>Atg8a</i>, is controlled in a complex manner by the anterior Hox paralog Lab (Labial), a master regulator of early development. <i>Atg8a</i> transcription is repressed in front of, while activated along, the MF by Lab. The amount of autophagic structures then remains elevated behind the moving MF. These results indicate that eye development in <i>Drosophila</i> depends on the cell death-suppressing and differentiating effects of the autophagic process. This novel, developmentally regulated function of autophagy in the morphogenesis of the compound eye may shed light on a more fundamental role for cellular self-digestion in differentiation and organ formation than previously thought.</p> <p><b>Abbreviations</b>: αTub84B, α-Tubulin at 84B; <i>Act5C, Actin5C</i>; AO, acridine orange; Atg, autophagy-related; Ato, Atonal; CASP3, caspase 3; Dcr-2; Dicer-2; Dfd, Deformed; DZ, differentiation zone; eGFP, enhanced green fluorescent protein; EM, electron microscopy; <i>exd, extradenticle; ey, eyeless</i>; FLP, flippase recombinase; FRT, FLP recognition target; <i>Gal4</i>, gene encoding the yeast transcription activator protein GAL4; GFP, green fluorescent protein; GMR, Glass multimer reporter; Hox, homeobox; <i>hth, homothorax; lab, labial</i>; L3F, L3 feeding larval stage; L3W, L3 wandering larval stage; lf, loss-of-function; MAP1LC3, microtubule-associated protein 1 light chain 3; MF, morphogenetic furrow; PE, phosphatidylethanolamine; PBS, phosphate-buffered saline; PI3K/PtdIns3K, class III phosphatidylinositol 3-kinase; PZ, proliferation zone; Ref(2)P, refractory to sigma P, RFP, red fluorescent protein; RNAi, RNA interference; RpL32, Ribosomal protein L32; RT-PCR, reverse transcription-coupled polymerase chain reaction; S.D., standard deviation; SQSTM1, Sequestosome-1, Tor, Target of rapamycin; TUNEL, terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay; UAS, upstream activation sequence; qPCR, quantitative real-time polymerase chain reaction; <i>w, white</i></p

AutophagyNet: high-resolution data source for the analysis of autophagy and its regulation

Macroautophagy/autophagy is a highly-conserved catabolic procss eliminating dysfunctional cellular components and invading pathogens. Autophagy malfunction contributes to disorders such as cancer, neurodegenerative and inflammatory diseases. Understanding autophagy regulation in health and disease has been the focus of the last decades. We previously provided an integrated database for autophagy research, the Autophagy Regulatory Network (ARN). For the last eight years, this resource has been used by thousands of users. Here, we present a new and upgraded resource, AutophagyNet. It builds on the previous database but contains major improvements to address user feedback and novel needs due to the advancement in omics data availability. AutophagyNet contains updated interaction curation and integration of over 280,000 experimentally verified interactions between core autophagy proteins and their protein, transcriptional and post-transcriptional regulators as well as their potential upstream pathway connections. AutophagyNet provides annotations for each core protein about their role: 1) in different types of autophagy (mitophagy, xenophagy, etc.); 2) in distinct stages of autophagy (initiation, expansion, termination, etc.); 3) with subcellular and tissue-specific localization. These annotations can be used to filter the dataset, providing customizable download options tailored to the user’s needs. The resource is available in various file formats (e.g. CSV, BioPAX and PSI-MI), and data can be analyzed and visualized directly in Cytoscape. The multi-layered regulation of autophagy can be analyzed by combining AutophagyNet with tissue- or cell type-specific (multi-)omics datasets (e.g. transcriptomic or proteomic data). The resource is publicly accessible at http://autophagynet.org. Abbreviations: ARN: Autophagy Regulatory Network; ATG: autophagy related; BCR: B cell receptor pathway; BECN1: beclin 1; GABARAP: GABA type A receptor-associated protein; IIP: innate immune pathway; LIR: LC3-interacting region; lncRNA: long non-coding RNA; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; miRNA: microRNA; NHR: nuclear hormone receptor; PTM: post-translational modification; RTK: receptor tyrosine kinase; TCR: T cell receptor; TLR: toll like receptor.</p