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1.
Cell Rep ; 25(11): 3110-3122.e6, 2018 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-30540943

RESUMO

Complete activation of B cells relies on their capacity to extract tethered antigens from immune synapses by either exerting mechanical forces or promoting their proteolytic degradation through lysosome secretion. Whether antigen extraction can also be tuned by local cues originating from the lymphoid microenvironment has not been investigated. We here show that the expression of Galectin-8-a glycan-binding protein found in the extracellular milieu, which regulates interactions between cells and matrix proteins-is increased within lymph nodes under inflammatory conditions where it enhances B cell arrest phases upon antigen recognition in vivo and promotes synapse formation during BCR recognition of immobilized antigens. Galectin-8 triggers a faster recruitment and secretion of lysosomes toward the B cell-antigen contact site, resulting in efficient extraction of immobilized antigens through a proteolytic mechanism. Thus, extracellular cues can determine how B cells sense and extract tethered antigens and thereby tune B cell responses in vivo.


Assuntos
Apresentação de Antígeno/imunologia , Antígenos de Superfície/metabolismo , Linfócitos B/imunologia , Galectinas/metabolismo , Sinapses Imunológicas/metabolismo , Animais , Linfócitos B/citologia , Pontos de Checagem do Ciclo Celular , Linhagem Celular , Galinhas , Linfonodos/metabolismo , Lisossomos/metabolismo , Camundongos Endogâmicos C57BL , Ligação Proteica , Proteólise , Ratos , Receptores de Antígenos de Linfócitos B/metabolismo , Linfócitos T/citologia
2.
PLoS One ; 9(2): e89641, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24586928

RESUMO

Drosophila melanogaster has been successfully used as a simple model to study the cellular and molecular mechanisms underlying behaviors, including the generation of motor programs. Thus, it has been shown that, as in vertebrates, CNS biogenic amines (BA) including serotonin (5HT) participate in motor control in Drosophila. Several evidence show that BA systems innervate an important association area in the insect brain previously associated to the planning and/or execution of motor programs, the Mushroom Bodies (MB). The main objective of this work is to evaluate the contribution of 5HT and its receptors expressed in MB to motor behavior in fly larva. Locomotion was evaluated using an automated tracking system, in Drosophila larvae (3(rd)-instar) exposed to drugs that affect the serotonergic neuronal transmission: alpha-methyl-L-dopa, MDMA and fluoxetine. In addition, animals expressing mutations in the 5HT biosynthetic enzymes or in any of the previously identified receptors for this amine (5HT1AR, 5HT1BR, 5HT2R and 5HT7R) were evaluated in their locomotion. Finally, RNAi directed to the Drosophila 5HT receptor transcripts were expressed in MB and the effect of this manipulation on motor behavior was assessed. Data obtained in the mutants and in animals exposed to the serotonergic drugs, suggest that 5HT systems are important regulators of motor programs in fly larvae. Studies carried out in animals pan-neuronally expressing the RNAi for each of the serotonergic receptors, support this idea and further suggest that CNS 5HT pathways play a role in motor control. Moreover, animals expressing an RNAi for 5HT1BR, 5HT2R and 5HT7R in MB show increased motor behavior, while no effect is observed when the RNAi for 5HT1AR is expressed in this region. Thus, our data suggest that CNS 5HT systems are involved in motor control, and that 5HT receptors expressed in MB differentially modulate motor programs in fly larvae.


Assuntos
Aminas Biogênicas/metabolismo , Locomoção/fisiologia , Corpos Pedunculados/metabolismo , Receptores de Serotonina/biossíntese , Animais , Proteínas de Drosophila/biossíntese , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Fluoxetina/farmacologia , Larva/fisiologia , Locomoção/efeitos dos fármacos , Interferência de RNA , Receptores de Serotonina/genética
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