Genetic interactions between<i>Drosophila melanogaster</i>Atg1 and paxillin reveal a role for paxillin in autophagosome formation

Chen, Guang-Chao; Lee, Janice Y.; Tang, Hong-Wen; Debnath, Jayanta; Thomas, Sheila M.; Settleman, Jeffrey

doi:10.4161/auto.5141

Cited by 58 publications

(63 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, it has been reported that vinculin and paxillin are released from FAs during nutrient deprivation. 36 We observed changes in cell morphology in cells plated on collagen I and uncoated substrate when they were incubated in nutrient-free medium. In contrast, no change in cell morphology and in the formation of FAs occurred during incubation in nutrient-free medium in cells plated on collagen IV.…”

Section: Resultsmentioning

confidence: 93%

Regulation of autophagy by extracellular matrix glycoproteins in HeLa cells

Tuloup-Minguez¹,

Greffard²,

Codogno³

et al. 2011

Autophagy

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 93%

Regulation of autophagy by extracellular matrix glycoproteins in HeLa cells

Tuloup-Minguez¹,

Greffard²,

Codogno³

et al. 2011

Autophagy

View full text Add to dashboard Cite

“…Another focal adhesion protein essential for autophagy is paxillin. Paxillin interacts with Atg1 in Drosophila (84). Paxillin is a target of YopH which dephosphorylates invasin-induced paxillin to disrupt focal adhesion complexes (85,86).…”

Section: Discussionmentioning

confidence: 99%

β1 Integrin-Dependent Engulfment of Yersinia enterocolitica by Macrophages Is Coupled to the Activation of Autophagy and Suppressed by Type III Protein Secretion

Deuretzbacher

Czymmeck

Reimer

et al. 2009

The Journal of Immunology

View full text Add to dashboard Cite

Autophagy is a central lysosomal degradation process that is essential for the maintenance of cellular homeostasis. Autophagy has furthermore emerged as integral part of the host immune response. Autophagic processes promote the separation and degradation of intracellular microorganisms which contributes to the development of innate and adaptive immunity. Some pathogenic microbes have therefore evolved mechanisms to evade or impede autophagy. We analyzed the effects of the enteropathogenic bacterium Yersinia enterocolitica on autophagy in macrophages. Yersiniae use a number of defined adhesins and secreted proteins to manipulate host immune responses. Our results showed that Y. enterocolitica defective in type III protein secretion efficiently activated autophagy in macrophages. Autophagy was mediated by the Yersinia adhesins invasin and YadA and particularly depended on the engagement of β1 integrin receptors. Several autophagy-related events followed β1 integrin-mediated engulfment of the bacteria including the formation of autophagosomes, processing of the marker protein LC3, redistribution of GFP-LC3 to bacteria-containing vacuoles, and the segregation of intracellular bacteria by autophagosomal compartments. These results provide direct evidence for the linkage of β1 integrin-mediated phagocytosis and autophagy induction. Multiple microbes signal through integrin receptors, and our results suggest a general principle by which the sensing of an extracellular microbe triggers autophagy. Owing to the importance of autophagy as host defense response, wild-type Y. enterocolitica suppressed autophagy by mobilizing type III protein secretion. The subversion of autophagy may be part of the Y. enterocolitica virulence strategy that supports bacterial survival when β1 integrin-dependent internalization and autophagy activation by macrophages are deleterious for the pathogen.

show abstract

“…When we examined MO-injected embryos at different stages of epiboly, there was no difference in the cell shape of the cells on the leading edge of epiboly (data not shown). Actin clumping and disorganization is often a byproduct of cell death ( 73,74 ). Since increased cell death has been reported in many mammalian tissues in response to loss of npc1 function, we examined epiboly-staged embryos for evidence of cell death.…”

Section: Npc1 Morphants That Complete Epiboly Display a Shorter Body mentioning

confidence: 99%

Requirement of Npc1 and availability of cholesterol for early embryonic cell movements in zebrafish

Schwend

Loucks

Snyder

et al. 2011

Journal of Lipid Research

View full text Add to dashboard Cite

This article is available online at http://www.jlr.org ( 1,2 ). NP-C symptoms typically appear in childhood, although infant onsets are possible. By the time the disorder's symptoms manifest, signifi cant cellular damage has already occurred. At the cellular level, NP-C is characterized by an aberrant accumulation of unesterifi ed cholesterol and glycolipids in the late endosomes and lysosomes of the endocytotic pathway ( 3-6 ). The disease is caused by mutations in one of two genes, Niemann-Pick disease, type C1 ( NPC1 ), which accounts for 95% of cases, or NiemannPick disease, type C2 ( NPC2 ), which accounts for 4% of cases. The remaining 1% of cases involves patients with confi rmed biochemical defects without an accompanying identifi ed mutation ( 7-10 ).The function of NPC1 involves regulating the movement of LDL-derived cholesterol and plasma-derived glycolipids from the endocytotic pathway to the endoplasmic reticulum/trans-Golgi network (ER/TGN) and the mitochondrial membrane ( 11-15 ). Despite reductions in sterol exit from the endocytotic pathway, NPC1-defi cient cells display normal sterol uptake, proper sterol delivery to the endocytotic organelles, and unperturbed levels of cholesterol ester hydrolysis ( 3,16,17 ). Excessive sterol content in the liver and spleen likely accounts for reports of hepato-splenomegaly, whereas sterol accumulation in the brain may contribute to the neurological deterioration in NP-C patients ( 16,(18)(19)(20).Abstract Niemann-Pick disease, type C (NP-C), often associated with Niemann-Pick disease, type C1 (NPC1) mutations, is a cholesterol-storage disorder characterized by cellular lipid accumulation, neurodegeneration, and reduced steroid production. To study NPC1 function in vivo, we cloned zebrafi sh npc1 and analyzed its gene expression and activity by reducing Npc1 protein with morpholino (MO)-oligonucleotides. Filipin staining in npc1-morphant cells was punctate, suggesting abnormal accumulation of cholesterol. Developmentally, reducing Npc1 did not disrupt early cell fate or survival; however, early morphogenetic movements were delayed, and the actin cytoskeleton network was abnormal. MO-induced defects were rescued with ectopic expression of mouse NPC1 , demonstrating functional gene conservation, and by treatments with steroids pregnenolone or dexamethasone, suggesting that reduced steroidogenesis contributed to abnormal cell movements. Cell death was found in anterior tissues of npc1 morphants at later stages, consistent with fi ndings in mammals. Collectively, these studies show that npc1 is required early for proper cell movement and cholesterol localization and later for cell survival. -Schwend, T., E. J. Loucks, D. Snyder, and S. C. Ahlgren. Requirement of Npc1 and availability of cholesterol for early embryonic cell movements in zebrafi sh. J.

show abstract

Genetic interactions betweenDrosophila melanogasterAtg1 and paxillin reveal a role for paxillin in autophagosome formation

Cited by 58 publications

References 41 publications

Regulation of autophagy by extracellular matrix glycoproteins in HeLa cells

Regulation of autophagy by extracellular matrix glycoproteins in HeLa cells

β1 Integrin-Dependent Engulfment of Yersinia enterocolitica by Macrophages Is Coupled to the Activation of Autophagy and Suppressed by Type III Protein Secretion

Requirement of Npc1 and availability of cholesterol for early embryonic cell movements in zebrafish

Contact Info

Product

Resources

About