| 1. |
- Bembenek, Joshua N., et al.
(författare)
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Meeting report - Cellular dynamics : membrane-cytoskeleton interface
- 2017
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Ingår i: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 130:17, s. 2775-2779
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Tidskriftsartikel (refereegranskat)abstract
- The first ever 'Cellular Dynamics' meeting on the membrane-cytoskeleton interface took place in Southbridge, MA on May 21-24, 2017 and was co-organized by Michael Way, Elizabeth Chen, Margaret Gardel and Jennifer Lippincott-Schwarz. Investigators from around the world studying a broad range of related topics shared their insights into the function and regulation of the cytoskeleton and membrane compartments. This provided great opportunities to learn about key questions in various cellular processes, from the basic organization and operation of the cell to higher-order interactions in adhesion, migration, metastasis, division and immune cell interactions in different model organisms. This unique and diverse mix of research interests created a stimulating and educational meeting that will hopefully continue to be a successful meeting for years to come.
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| 2. |
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| 3. |
- Jayaram, Satish Arcot, 1979-, et al.
(författare)
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COPI Vesicle Transport Is a Common Requirement for Tube Expansion in Drosophila
- 2008
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 09 Apr
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Tidskriftsartikel (refereegranskat)abstract
- Background Tube expansion defects like stenoses and atresias cause devastating human diseases. Luminal expansion during organogenesis begins to be elucidated in several systems but we still lack a mechanistic view of the process in many organs. The Drosophila tracheal respiratory system provides an amenable model to study tube size regulation. In the trachea, COPII anterograde transport of luminal proteins is required for extracellular matrix assembly and the concurrent tube expansion. Principal Findings We identified and analyzed Drosophila COPI retrograde transport mutants with narrow tracheal tubes. γCOP mutants fail to efficiently secrete luminal components and assemble the luminal chitinous matrix during tracheal tube expansion. Likewise, tube extension is defective in salivary glands, where it also coincides with a failure in the luminal deposition and assembly of a distinct, transient intraluminal matrix. Drosophila γCOP colocalizes with cis-Golgi markers and in γCOP mutant embryos the ER and Golgi structures are severely disrupted. Analysis of γCOP and Sar1 double mutants suggests that bidirectional ER-Golgi traffic maintains the ER and Golgi compartments and is required for secretion and assembly of luminal matrixes during tube expansion. Conclusions/Significance Our results demonstrate the function of COPI components in organ morphogenesis and highlight the common role of apical secretion and assembly of transient organotypic matrices in tube expansion. Intraluminal matrices have been detected in the notochord of ascidians and zebrafish COPI mutants show defects in notochord expansion. Thus, the programmed deposition and growth of distinct luminal molds may provide distending forces during tube expansion in diverse organs.
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| 6. |
- Liu, Dan, 1987-
(författare)
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Reciprocal regulation of endocytosis and signaling in Drosophila epithelial development and aberrant growth
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Endocytosis and subsequent endosomal sorting of plasma membrane proteins and nutrients are essential for cellular homeostasis. Previous work has uncovered several different internalization mechanisms, endosomal sorting routes and aspects of their regulation. Endocytosis components have also been variably implicated in signaling activation or silencing, but the underlying mechanisms of how endocytosis and signaling are coordinated in epithelial tissues remain obscure. We have characterized an endocytic regulatory circuit, where type III receptor tyrosine phosphatases (RPTPs) antagonize the non-receptor tyrosine kinase Btk29A in phosphorylating the actin nucleation promoting factor WASH. Btk29A phosphorylates a conserved tyrosine motif in WASH (Y273) and this modification is sufficient to induce endosomal actin polymerization both in Drosophila airways and in mammalian cultured cells. The phospho-WASH-induced actin polymerization promotes apical protein internalization and destabilizes cortical actin altering epithelial cell and organ shapes. To investigate the function of the Ptp10D/Btk29A/WASH circuit in the context of proliferating cells, we turned to a model of tumor-suppressive cell competition in Drosophila imaginal eye discs. Clones of polarity-deficient (scrib-) epithelial cells are normally eliminated from the eye discs but overgrow when Ptp10D is also inactivated in the clones. We found that constitutive WASH phosphorylation on Y273 is sufficient to induce Yki activation and epidermal growth factor receptor (EGFR) signaling, leading to clone overgrowth. To understand how endosomal phospho-WASH may induce EGFR signaling, we investigated the endocytic routes of EGFR and Ptp10D. EGFR is recycled from endosomes to the plasma membrane by the retriever/WASH complex but Ptp10D utilizes the retromer/WASH complex. The dysregulated WASH phosphorylation results in the separation of EGFR from its inhibitor, Ptp10D, in endosomes leading to EGFR signaling upregulation and aberrant clonal growth. We showed that WASH phosphorylation is regulated in the retromer-enriched microdomain by the Stit and Insulin receptors, which antagonize Ptp10D. In turn, retromer function is required for Stit recycling suggesting a positive feedback loop between metabolism and retromer trafficking through WASH phosphorylation. Imbalances in this regulatory loop can lead to the overgrowth of polarity-deficient epithelial cells.
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| 7. |
- Liu, Dan, et al.
(författare)
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WASH activation controls endosomal recycling and EGFR and Hippo signaling during tumor-suppressive cell competition
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Cell competition is a conserved homeostatic mechanism whereby epithelial cells eliminate neighbors with lower fitness. Cell communication at the interface of wild-type winner cells and polarity-deficient (scrib-/-) losers is established through Sas-mediated Ptp10D activation in polarity-deficient cells. This tumor-suppressive cell competition restrains EGFR and Hippo signaling and enables Eiger-JNK mediated apoptosis in scrib-/- clones. Here, we show that the activation state of the endosomal actin regulator WASH is a central node linking EGFR and Hippo signaling activation. The tyrosine kinase Btk29A and its substrate WASH are required downstream of Ptp10D for loser cell elimination. Constitutively active, phosphomimetic WASH is sufficient to induce both EGFR and Yki activation leading to overgrowth. On the mechanistic level we show that Ptp10D is recycled by the WASH/retromer complex, while EGFR is recycled by the WASH/retriever complex. Constitutive WASH activation selectively interferes with retromer function leading to Ptp10D mistargeting while promoting EGFR recycling and signaling activation. Phospho-WASH also activates aberrant Arp2/3 actin polymerization, leading to cytoskeletal imbalance, Yki activation and reduced apoptosis. Selective manipulation of WASH phosphorylation on sorting endosomes may restrict epithelial tumorous growth.
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| 8. |
- Moretti, Chiara H., et al.
(författare)
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Dietary nitrite extends lifespan and prevents age-related locomotor decline in the fruit fly
- 2020
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Ingår i: Free Radical Biology & Medicine. - : Elsevier BV. - 0891-5849 .- 1873-4596. ; 160, s. 860-870
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Tidskriftsartikel (refereegranskat)abstract
- Aging is associated with decreased nitric oxide (NO) bioavailability and signalling. Boosting of a dietary nitrate nitrite-NO pathway e.g. by ingestion of leafy green vegetables, improves cardiometabolic function, mitochondrial efficiency and reduces oxidative stress in humans and rodents, making dietary nitrate and nitrite an appealing intervention to address age-related disorders. On the other hand, these anions have long been implicated in detrimental health effects of our diet, particularly in formation of carcinogenic nitrosamines.The aim of this study was to assess whether inorganic nitrite affects lifespan in Drosophila melanogaster and investigate possible mechanisms underlying any such effect.In a survival assay, female flies fed a nitrite supplemented diet showed lifespan extension by 9 and 15% with 0.1 and 1 mu M nitrite respectively, with no impact of nitrite on reproductive output. Interestingly, nitrite could also protect female flies from age-dependent locomotor decline, indicating a protective effect on healthspan. NO generation from nitrite involved Drosophila commensal bacteria and was indicated by a fluorescent probe as well as direct measurements of NO gas formation with chemiluminescence.Nutrient sensing pathways such as TOR and sirtuins, have been strongly implicated in lifespan extension. In aged flies, nitrite supplementation significantly downregulated dTOR and upregulated dSir2 gene expression. Total triglycerides and glucose were decreased, a described downstream effect of both TOR and sirtuin pathways.In conclusion, we demonstrate that very low doses of dietary nitrite extend lifespan and favour healthspan in female flies. We propose modulation of nutrient sensing pathways as driving mechanisms for such effects.
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| 9. |
- Pinheiro, Ana Sofia, 1988-, et al.
(författare)
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Scavenger receptor endocytosis controls apical membrane morphogenesis in the Drosophila airways
- 2023
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Ingår i: ELIFE. - 2050-084X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- The acquisition of distinct branch sizes and shapes is a central aspect in tubular organ morphogenesis and function. In the Drosophila airway tree, the interplay of apical extracellular matrix (ECM) components with the underlying membrane and cytoskeleton controls tube elongation, but the link between ECM composition with apical membrane morphogenesis and tube size regulation is elusive. Here, we characterized Emp (epithelial membrane protein), a Drosophila CD36 homolog belonging to the scavenger receptor class B protein family. emp mutant embryos fail to internalize the luminal chitin deacetylases Serp and Verm at the final stages of airway maturation and die at hatching with liquid filled airways. Emp localizes in apical epithelial membranes and shows cargo selectivity for LDLr-domain containing proteins. emp mutants also display over elongated tracheal tubes with increased levels of the apical proteins Crb, DE-cad, and phosphorylated Src (p-Src). We show that Emp associates with and organizes the beta H-Spectrin cytoskeleton and is itself confined by apical F-actin bundles. Overexpression or loss of its cargo protein Serp lead to abnormal apical accumulations of Emp and perturbations in p-Src levels. We propose that during morphogenesis, Emp senses and responds to luminal cargo levels by initiating apical membrane endocytosis along the longitudinal tube axis and thereby restricts airway elongation.
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| 10. |
- Ronnberg-Wastljung, Ann-Christin, et al.
(författare)
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Resistance to Melampsora larici-epitea leaf rust in Salix : analyses of quantitative trait loci
- 2008
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Ingår i: Journal of Applied Genetics. - 1234-1983 .- 2190-3883. ; 49:4, s. 321-331
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Tidskriftsartikel (refereegranskat)abstract
- Quantitative resistance of Salix to Melampsora larici--epitea leaf rust was studied in 2 Salix mapping populations. One population was a backcross between a S, schwerinii x S. viminalis hybrid and S. viminalis, and the other was all F-2 population between S. viminalis and S. dasyclados. A leaf disc bioassay was used to study the components of quantitative resistance (latent period, uredinia number, and uredinia size) to 3 isolates of the leaf rust. The analysis of quantitative trait loci (QTLs) revealed 9 genomic regions in the backcross population and 7 genomic regions in the F-2 population that were important for rust resistance, with QTLs explaining 8-26% of the phenotypic variation. An important genomic region was identified for the backcross population in linkage group 2, where QTLs were identified for all resistance components for 2 of the rust isolates. Four of the QTLs had overlapping mapping intervals, demonstrating a common genetic background for latent period, uredinia diameter, and uredinia number. QTLs specific to some rust isolates and to some resistance components were also found, indicating a combination of common and specific mechanisms involved in the various resistance components. Breeding implications in relation to these findings are discussed.
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