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1.
Trends Neurosci ; 46(7): 525-538, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37202301

RESUMO

RNA granules are dynamic entities controlling the spatiotemporal distribution and translation of RNA molecules. In neurons, a variety of RNA granules exist both in the soma and in cellular processes. They contain transcripts encoding signaling and synaptic proteins as well as RNA-binding proteins causally linked to several neurological disorders. In this review, we highlight that neuronal RNA granules exhibit properties of biomolecular condensates that are regulated upon maturation and physiological aging and how they are reversibly remodeled in response to neuronal activity to control local protein synthesis and ultimately synaptic plasticity. Moreover, we propose a framework of how neuronal RNA granules mature over time in healthy conditions and how they transition into pathological inclusions in the context of late-onset neurodegenerative diseases.


Assuntos
Grânulos Citoplasmáticos , Neurônios , Humanos , Grânulos Citoplasmáticos/metabolismo , Neurônios/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Grânulos de Ribonucleoproteínas Citoplasmáticas , Plasticidade Neuronal/fisiologia , RNA/metabolismo
2.
Biochimie ; 112: 41-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25731714

RESUMO

The triatomine insect, Rhodnius prolixus, is a vector of Trypanosoma cruzi, a protozoan parasite that causes Chagas disease. The parasite must overcome immune response and microbiota to develop inside the midgut of triatomines. In this study, we expressed, purified and characterized a Kazal-type inhibitor from the midgut of R. prolixus, named RpTI, which may be involved in microbiota - T. cruzi interactions. The qPCR showed that the RpTI transcript was primarily expressed in tissues from the intestinal tract and that it was upregulated in the anterior midgut after T. cruzi infection. A 315-bp cDNA fragment encoding the mature protein was cloned into the pPIC9 vector and expressed in Pichia pastoris system. Recombinant RpTI (rRpTI) was purified on a trypsin-Sepharose column and had a molecular mass of 11.5 kDa as determined by SDS-PAGE analysis. This protein inhibited trypsin (Ki = 0.42 nM), whereas serine proteases from the coagulation cascade were not inhibited. Moreover, trypanocidal assays revealed that rRpTI did not interfere in the viability of T. cruzi trypomastigotes. The RpTI transcript was also knocked down by RNA interference prior to infection of R. prolixus with T. cruzi. The amount of T. cruzi in the anterior midgut was significantly lower in RpTI knockdown insects compared to the non-silenced groups. We also verified that the bacterial load is higher in the anterior midgut of silenced and infected R. prolixus compared to non-silenced and infected insects. Our results suggest that T. cruzi infection increases the expression of RpTI to mediate microbiota modulation and is important for parasite immediately after infection with R. prolixus.


Assuntos
Proteínas de Insetos , Insetos Vetores , Intestinos/microbiologia , Microbiota , Rhodnius , Trypanosoma cruzi/metabolismo , Inibidor da Tripsina Pancreática de Kazal , Animais , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Insetos Vetores/genética , Insetos Vetores/metabolismo , Insetos Vetores/microbiologia , Rhodnius/genética , Rhodnius/metabolismo , Rhodnius/microbiologia , Inibidor da Tripsina Pancreática de Kazal/genética , Inibidor da Tripsina Pancreática de Kazal/metabolismo
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