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1.
Traffic ; 23(7): 374-390, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35575181

RESUMO

E-cadherin has a fundamental role in epithelial tissues by providing cell-cell adhesion. Polarised E-cadherin exocytosis to the lateral plasma membrane is central for cell polarity and epithelial homeostasis. Loss of E-cadherin secretion compromises tissue integrity and is a prerequisite for metastasis. Despite this pivotal role of E-cadherin secretion, the transport mechanism is still unknown. Here we identify Myosin V as the motor for E-cadherin secretion. Our data reveal that Myosin V and F-actin are required for the formation of a continuous apicolateral E-cadherin belt, the zonula adherens. We show by live imaging how Myosin V transports E-cadherin vesicles to the plasma membrane, and distinguish two distinct transport tracks: an apical actin network leading to the zonula adherens and parallel actin bundles leading to the basal-most region of the lateral membrane. E-cadherin secretion starts in endosomes, where Rab11 and Sec15 recruit Myosin V for transport to the zonula adherens. We also shed light on the endosomal sorting of E-cadherin by showing how Rab7 and Snx16 cooperate in moving E-cadherin into the Rab11 compartment. Thus, our data help to understand how polarised E-cadherin secretion maintains epithelial architecture and prevents metastasis.


Assuntos
Caderinas/metabolismo , Miosina Tipo V/metabolismo , Actinas/metabolismo , Junções Aderentes/metabolismo , Animais , Adesão Celular , Endossomos/metabolismo , Exocitose , Humanos , Metástase Neoplásica/prevenção & controle
2.
Dev Biol ; 452(2): 83-94, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31085193

RESUMO

The proliferation, differentiation and function of immune cells in vertebrates, as well as in the invertebrates, is regulated by distinct signalling pathways and crosstalk with systemic and cellular metabolism. We have identified the Lime gene (Linking Immunity and Metabolism, CG18446) as one such connecting factor, linking hemocyte development with systemic metabolism in Drosophila. Lime is expressed in larval plasmatocytes and the fat body and regulates immune cell type and number by influencing the size of hemocyte progenitor populations in the lymph gland and in circulation. Lime mutant larvae exhibit low levels of glycogen and trehalose energy reserves and they develop low number of hemocytes. The low number of hemocytes in Lime mutants can be rescued by Lime overexpression in the fat body. It is well known that immune cell metabolism is tightly regulated with the progress of infection and it must be supported by systemic metabolic changes. Here we demonstrate that Lime mutants fails to induce such systemic metabolic changes essential for the larval immune response. Indeed, Lime mutants are not able to sustain high numbers of circulating hemocytes and are compromised in the number of lamellocytes produced during immune system challenge, using a parasitic wasp infection model. We therefore propose the Lime gene as a novel functional link between systemic metabolism and Drosophila immunity.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/imunologia , Drosophila melanogaster/metabolismo , Imunidade , Proteínas Nucleares/metabolismo , Animais , Diferenciação Celular , Metabolismo Energético , Corpo Adiposo/metabolismo , Hemócitos/citologia , Hemócitos/metabolismo , Larva/metabolismo , Tecido Linfoide/metabolismo , Mutação/genética
3.
Biointerphases ; 12(5): 05G607, 2017 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-29113436

RESUMO

Developing novel compounds with antimicrobial properties can be an effective approach to decreasing the number of healthcare-associated infections, particularly in the context of medical devices and touch surfaces. A variety of molybdate powders (Ag2MoO4, CaMoO4, CuMoO4 and Cu3Mo2O9) were synthesized and characterized, and Escherichia coli was used as a model gram-negative bacterium to demonstrate their antimicrobial properties. Optical density measurements, bacterial colony growth, and stained gel images for protein expression clearly showed that silver- and copper molybdates inhibit bacterial growth, whereas CaMoO4 exhibited no bactericidal effect. All tests were performed in both daylight and darkness to assess the possible contribution of a photocatalytic effect on the activity observed. The main mechanism responsible for the antibacterial effect observed for Ag2MoO4 is related to Ag+ release in combination with medium acidification, whereas for compounds containing copper, leaching of Cu2+ ions is proposed. All these effects are known to cause damage at the cellular level. A photocatalytic contribution to the antibacterial activity was not clearly observable. Based on the pH and solubility measurements performed for powders in contact with various media (ultrapure water and bacterial growth medium), silver molybdate (Ag2MoO4) was identified as the best antibacterial candidate. This compound has great potential for further use in hybrid powder-polymer/varnish systems for touch surfaces in healthcare settings.


Assuntos
Antibacterianos/farmacologia , Cálcio/farmacologia , Cobre/farmacologia , Escherichia coli/efeitos dos fármacos , Molibdênio/farmacologia , Prata/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Cálcio/química , Cobre/química , Escherichia coli/crescimento & desenvolvimento , Concentração de Íons de Hidrogênio , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Molibdênio/química , Prata/química , Solubilidade
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