Tail-anchored (TA) proteins contain a single transmembrane domain (TMD) at the C-terminus that anchors them to the membranes of organelles where they mediate critical cellular processes. Accordingly, mutations in genes encoding TA proteins have been identified in a number of severe inherited disorders. Despite the importance of correctly targeting a TA protein to its appropriate membrane, the mechanisms and signals involved are not fully understood. In this study, we identify additional peroxisomal TA proteins, discover more proteins that are present on multiple organelles, and reveal that a combination of TMD hydrophobicity and tail charge determines targeting to distinct organelle locations in mammals. Specifically, an increase in tail charge can override a hydrophobic TMD signal and re-direct a protein from the ER to peroxisomes or mitochondria and vice versa. We show that subtle changes in those parameters can shift TA proteins between organelles, explaining why peroxisomes and mitochondria have many of the same TA proteins. This enabled us to associate characteristic physicochemical parameters in TA proteins with particular organelle groups. Using this classification allowed successful prediction of the location of uncharacterized TA proteins for the first time.
The human cytomegalovirus developed distinct evasion mechanisms from the cellular antiviral response involving vMIA, a virally-encoded protein that is not only able to prevent cellular apoptosis but also to inhibit signalling downstream from mitochondrial MAVS. vMIA has been shown to localize at mitochondria and to trigger their fragmentation, a phenomenon proven to be essential for the signalling inhibition. Here, we demonstrate that vMIA is also localized at peroxisomes, induces their fragmentation and inhibits the peroxisomal-dependent antiviral signalling pathway. Importantly, we demonstrate that peroxisomal fragmentation is not essential for vMIA to specifically inhibit signalling downstream the peroxisomal MAVS. We also show that vMIA interacts with the cytoplasmic chaperone Pex19, suggesting that the virus has developed a strategy to highjack the peroxisomal membrane proteins’ transport machinery. Furthermore, we show that vMIA is able to specifically interact with the peroxisomal MAVS. Our results demonstrate that peroxisomes constitute a platform for evasion of the cellular antiviral response and that the human cytomegalovirus has developed a mechanism by which it is able to specifically evade the peroxisomal MAVS-dependent antiviral signalling.
Pex11 proteins are involved in membrane elongation and division processes associated with the multiplication of peroxisomes. Human Pex11pβ has recently been linked to a new disorder affecting peroxisome morphology and dynamics. Here, we have analyzed the exact membrane topology of Pex11pβ. Studies with an epitope-specific antibody and protease protection assays show that Pex11pβ is an integral membrane protein with two transmembrane domains flanking an internal region exposed to the peroxisomal matrix and N- and C-termini facing the cytosol. A glycine-rich internal region within Pex11pβ is dispensable for peroxisome membrane elongation and division. However, we demonstrate that an amphipathic helix (Helix 2) within the first N-terminal 40 amino acids is crucial for membrane elongation and self-interaction of Pex11pβ. Interestingly, we find that Pex11pβ self-interaction strongly depends on the detergent used for solubilization. We also show that N-terminal cysteines are not essential for membrane elongation, and that putative N-terminal phosphorylation sites are dispensable for Pex11pβ function. We propose that self-interaction of Pex11pβ regulates its membrane deforming activity in conjunction with membrane lipids.
This article aims to contribute to the growing body of literature that critically reflects on the practical, ethical and relational challenges raised by conducting research in prison. Basing our work on three different studies developed in Portuguese prison settings, we develop an intersectional understanding of building (dis) trust in prison settings by reflecting upon researchers' characteristics and relational dynamics with people in the field, whether they are professionals or prisoners.
The main purpose of this article is to discuss some ethical-methodological issues associated with scientific research in confinement settings, particularly those that result from the relationship with the confined individual in the framework of qualitative research. Basing the reflection on empirical research developed by both authors in Portuguese confinement settings – prisons and youth educational centres – we examine the significant challenges and dilemmas this type of research entails, exploring the interface between procedural ethics and ethics in practice at three points in the analytical process: before, during and after data collection. This article illustrates the interplay between formal and informal procedures, and between the initial distancing and strangeness when making contact with confinement settings and their social actors and the institutional and relational dynamics that become ingrained in our everyday practice. Our goal is to give visibility to these institutional and relational dynamics and to reflect on the challenges experienced by those who enter confinement settings to do research, in an effort to make the research process more transparent and at the same time more reflexive. We end our reflection advocating more ethically committed and critical scientific research.
A construção do pânico moral sobre os ciganos e os imigrantes na imprensa diária portuguesa Sílvia Gomes 1 Resumo: Neste artigo analisa-se os discursos e representações veiculados pela imprensa diária portuguesa acerca da criminalidade associada a grupos imigrantes ou étnicos. A partir desta análise, pretende-se mostrar como as narrativas que circulam na imprensa transmitem visões sobre a ordem social, que promovem o consenso e o controle social-através da ênfase exagerada sobre o risco de vitimização-e contribuem para a construção do designado "pânico moral". A mediatização da criminalidade produz visões amplamente partilhadas e consensuais, ao mesmo tempo que alimenta, junto do público em geral, visões estereotipadas sobre os "criminosos", podendo associar determinado tipo de criminalidade aos grupos socialmente excluídos e grupos étnicos, tais como ciganos e imigrantes. Esses estereótipos podem converter estes grupos em ameaças potenciais para os interesses e valores vigentes na sociedade, através da produção de cruzadas morais que, pela reação emocional desproporcionada e excessiva que desperta no público, representam os porta-vozes da moralidade e os seus diagnósticos e soluções. Este artigo discute a cobertura da imprensa portuguesa nos casos da criminalidade perpetrada por ciganos e imigrantes como um exemplo paradigmático de um produto de uma indústria cultural. Essas narrativas mediáticas são incitadas por lógicas globais de mercantilização da esfera pública, com base na criminalização da pobreza e no medo de populações urbanas consideradas "problemáticas", cujo objetivo é aumentar a ligação emocional por parte do público e, assim, levar às referidas cruzadas morais.
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