Proteasome inhibition triggers tissue-specific immune responses against different pathogens in < i > C < /i > . < i > elegans < /i >
We report here that, in contrast to the previously reported role of SKN-1 in promoting resistance against bacterial infection, loss-of-function mutants inskn-1a and its activating enzymesddi-1 andpng-1 show constitutive expression of immune response programs against natural eukaryotic pathogens ofC.elegans. These programs are the oomycete recognition response (ORR), which promotes resistance against oomycetes that infect through the epidermis, and the intracellular pathogen response (IPR), which promotes resistance against intestine-infecting microsporidia. Consequently,skn-1a mutants show increased resistance to both oomy...
Source: PLoS Biology: Archived Table of Contents - March 11, 2024 Category: Biology Authors: Manish Grover Source Type: research

An ancient bacterial zinc acquisition system identified from a cyanobacterial exoproteome
by Cristina Sarasa-Buisan, Jes ús A. G. Ochoa de Alda, Cristina Velázquez-Suárez, Miguel Ángel Rubio, Guadalupe Gómez-Baena, María F. Fillat, Ignacio Luque Bacteria have developed fine-tuned responses to cope with potential zinc limitation. The Zur protein is a key player in coordinating this response in most species. Comparative proteomics conducted on the cyanobacteriumAnabaena highlighted the more abundant proteins in azur mutant compared to the wild type. Experimental evidence showed that the exoprotein ZepA mediates zinc uptake. Genomic context of thezepA gene and protein structure prediction provided additiona...
Source: PLoS Biology: Archived Table of Contents - March 11, 2024 Category: Biology Authors: Cristina Sarasa-Buisan Source Type: research

IntAct: A nondisruptive internal tagging strategy to study the organization and function of actin isoforms
by Maxime C. van Zwam, Anubhav Dhar, Willem Bosman, Wendy van Straaten, Suzanne Weijers, Emiel Seta, Ben Joosten, Jeffrey van Haren, Saravanan Palani, Koen van den Dries Mammals have 6 highly conserved actin isoforms with nonredundant biological functions. The molecular basis of isoform specificity, however, remains elusive due to a lack of tools. Here, we describe the development of IntAct, an internal tagging strategy to study actin isoforms in fixed and living cells. We identified a residue pair in β-actin that permits tag integration and used knock-in cell lines to demonstrate that IntAct β-actin expression and fila...
Source: PLoS Biology: Archived Table of Contents - March 11, 2024 Category: Biology Authors: Maxime C. van Zwam Source Type: research

FAM81A is a postsynaptic protein that regulates the condensation of postsynaptic proteins via liquid –liquid phase separation
In this study, we conducted a comprehensive meta-analysis of 35 PSD proteome datasets, encompassing a total of 5,869 proteins. Employing a ranking methodology, we identified 97 proteins that remain inadequately characterized. From this selection, we focused our detailed analysis on the highest-ranked protein, FAM81A. FAM81A interacts with PSD proteins, including PSD-95, SynGAP, and NMDA receptors, and promotes liquid –liquid phase separation of those proteins in cultured cells or in vitro. Down-regulation of FAM81A in cultured neurons causes a decrease in the size of PSD-95 puncta and the frequency of neuronal firing. Ou...
Source: PLoS Biology: Archived Table of Contents - March 7, 2024 Category: Biology Authors: Takeshi Kaizuka Source Type: research

Role for gene conversion in the evolution of cell-surface antigens of the malaria parasite < i > Plasmodium falciparum < /i >
In this study, we analysed the genetic diversity of 2 of the most var iable MSPs, DBLMSP and DBLMSP2, which are paralogs (descended from an ancestral duplication). Despite thousands of available Illumina WGS datasets from malaria-endemic countries, diversity in these genes has been hard to characterise as reads containing highly diverged alleles completely fail to ali gn to the reference genome. To solve this, we developed a pipeline leveraging genome graphs, enabling us to genotype them at high accuracy and completeness. Using our newly- resolved sequences, we found that both genes exhibit 2 deeply diverged lineages in a ...
Source: PLoS Biology: Archived Table of Contents - March 7, 2024 Category: Biology Authors: Brice Letcher Source Type: research

Degrade to stay healthy —Proteolytic interplay during inflammation
by Christian M ünz Proteasomes and autophagy constitute the 2 main proteolytic machineries for cytoplasmic content. A new study in PLOS Biology now demonstrates that autophagy stimulation alters proteasome composition, degrading hyperactive immunoproteasomes and thereby limiting inflammation. Proteasomes and autophagy constitute the two main proteolytic machineries for cytoplasmic content. This Primer explores a new study in PLOS Biology which demonstrates that autophagy stimulation alters proteasome composition, degrading hyperactive immunoproteasomes and thereby limiting inflammation. (Source: PLoS Biology: Archived Table of Contents)
Source: PLoS Biology: Archived Table of Contents - March 7, 2024 Category: Biology Authors: Christian M ünz Source Type: research

Pharmacological induction of autophagy reduces inflammation in macrophages by degrading immunoproteasome subunits
by Jiao Zhou, Chunxia Li, Meng Lu, Gaoyue Jiang, Shanze Chen, Huihui Li, Kefeng Lu Defective autophagy is linked to proinflammatory diseases. However, the mechanisms by which autophagy limits inflammation remain elusive. Here, we found that the pan-FGFR inhibitor LY2874455 efficiently activated autophagy and suppressed expression of proinflammatory factors in macrophages stimulated by lipopolysaccharide (LPS). Multiplex proteomic profiling identified the immunoproteasome, which is a specific isoform of the 20s constitutive proteasome, as a substrate that is degraded by selective autophagy. SQSTM1/p62 was found to be a sel...
Source: PLoS Biology: Archived Table of Contents - March 6, 2024 Category: Biology Authors: Jiao Zhou Source Type: research

Cep131-Cep162 and Cby-Fam92 complexes cooperatively maintain Cep290 at the basal body and contribute to ciliogenesis initiation
by Zhimao Wu, Huicheng Chen, Yingying Zhang, Yaru Wang, Qiaoling Wang, C éline Augière, Yanan Hou, Yuejun Fu, Ying Peng, Bénédicte Durand, Qing Wei Cilia play critical roles in cell signal transduction and organ development. Defects in cilia function result in a variety of genetic disorders. Cep290 is an evolutionarily conserved ciliopathy protein that bridges the ciliary membrane and axoneme at the basal body (BB) and plays critical roles in the initiation of ciliogenesis and TZ assembly. How Cep290 is maintained at BB and whether axonemal and ciliary membrane localized cues converge to determine the localization of ...
Source: PLoS Biology: Archived Table of Contents - March 5, 2024 Category: Biology Authors: Zhimao Wu Source Type: research

Cross-frequency coupling in cortico-hippocampal networks supports the maintenance of sequential auditory information in short-term memory
by Arthur Borderie, Anne Caclin, Jean-Philippe Lachaux, Marcela Perrone-Bertollotti, Roxane S. Hoyer, Philippe Kahane, H élène Catenoix, Barbara Tillmann, Philippe Albouy It has been suggested that cross-frequency coupling in cortico-hippocampal networks enables the maintenance of multiple visuo-spatial items in working memory. However, whether this mechanism acts as a global neural code for memory retention across sensory modalities remains to be demonstrated. Intracranial EEG data were recorded while drug-resistant patients with epilepsy performed a delayed matched-to-sample task with tone sequences. We manipulated ta...
Source: PLoS Biology: Archived Table of Contents - March 5, 2024 Category: Biology Authors: Arthur Borderie Source Type: research

An engineered bacterial symbiont allows noninvasive biosensing of the honey bee gut environment
by Audam Chhun, Silvia Moriano-Gutierrez, Florian Zoppi, Am élie Cabirol, Philipp Engel, Yolanda Schaerli The honey bee is a powerful model system to probe host –gut microbiota interactions, and an important pollinator species for natural ecosystems and for agriculture. While bacterial biosensors can provide critical insight into the complex interplay occurring between a host and its associated microbiota, the lack of methods to noninvasively sample the g ut content, and the limited genetic tools to engineer symbionts, have so far hindered their development in honey bees. Here, we built a versatile molecular tool kit t...
Source: PLoS Biology: Archived Table of Contents - March 5, 2024 Category: Biology Authors: Audam Chhun Source Type: research

Viral regulation of organelle membrane contact sites
by William A. Hofstadter, Elene Tsopurashvili, Ileana M. Cristea At the core of organelle functions lies their ability and need to form dynamic organelle –organelle networks that drive intracellular communication and coordination of cellular pathways. These networks are facilitated by membrane contact sites (MCSs) that promote both intra-organelle and inter-organelle communication. Given their multiple functions, MCSs and the proteins that form the m are commonly co-opted by viruses during infection to promote viral replication. This Essay discusses mechanisms acquired by diverse human viruses to regulate MCS functions ...
Source: PLoS Biology: Archived Table of Contents - March 5, 2024 Category: Biology Authors: William A. Hofstadter Source Type: research

An adapted MS2-MCP system to visualize endogenous cytoplasmic mRNA with live imaging in < i > Caenorhabditis elegans < /i >
by Cristina Tocchini, Susan E. Mango Live imaging of RNA molecules constitutes an invaluable means to track the dynamics of mRNAs, but live imaging inCaenorhabditis elegans has been difficult to achieve. Endogenous transcripts have been observed in nuclei, but endogenous mRNAs have not been detected in the cytoplasm, and functional mRNAs have not been generated. Here, we have adapted live imaging methods to visualize mRNA in embryonic cells. We have tagged endogenous transcripts with MS2 hairpins in the 3 ′ untranslated region (UTR) and visualized them after adjusting MS2 Coat Protein (MCP) expression. A reduced number ...
Source: PLoS Biology: Archived Table of Contents - March 1, 2024 Category: Biology Authors: Cristina Tocchini Source Type: research

Structural and functional characterization of AfsR, an SARP family transcriptional activator of antibiotic biosynthesis in < i > Streptomyces < /i >
by Yiqun Wang, Xu Yang, Feng Yu, Zixin Deng, Shuangjun Lin, Jianting ZhengStreptomyces antibiotic regulatory proteins (SARPs) are widely distributed activators of antibiotic biosynthesis.Streptomyces coelicolor AfsR is an SARP regulator with an additional nucleotide-binding oligomerization domain (NOD) and a tetratricopeptide repeat (TPR) domain. Here, we present cryo-electron microscopy (cryo-EM) structures and in vitro assays to demonstrate how the SARP domain activates transcription and how it is modulated by NOD and TPR domains. The structures of transcription initiation complexes (TICs) show that the SARP domain forms...
Source: PLoS Biology: Archived Table of Contents - March 1, 2024 Category: Biology Authors: Yiqun Wang Source Type: research

Value-related learning in the olfactory bulb occurs through pathway-dependent perisomatic inhibition of mitral cells
by Sander Lindeman, Xiaochen Fu, Janine Kristin Reinert, Izumi Fukunaga Associating values to environmental cues is a critical aspect of learning from experiences, allowing animals to predict and maximise future rewards. Value-related signals in the brain were once considered a property of higher sensory regions, but their wide distribution across many brain regions is increasingly recognised. Here, we investigate how reward-related signals begin to be incorporated, mechanistically, at the earliest stage of olfactory processing, namely, in the olfactory bulb. In head-fixed mice performing Go/No-Go discrimination of closel...
Source: PLoS Biology: Archived Table of Contents - March 1, 2024 Category: Biology Authors: Sander Lindeman Source Type: research

ReptiLearn: An automated home cage system for behavioral experiments in reptiles without human intervention
by Tal Eisenberg, Mark Shein-Idelson Understanding behavior and its evolutionary underpinnings is crucial for unraveling the complexities of brain function. Traditional approaches strive to reduce behavioral complexity by designing short-term, highly constrained behavioral tasks with dichotomous choices in which animals respond to defined external perturbation. In contrast, natural behaviors evolve over multiple time scales during which actions are selected through bidirectional interactions with the environment and without human intervention. Recent technological advancements have opened up new possibilities for experime...
Source: PLoS Biology: Archived Table of Contents - February 29, 2024 Category: Biology Authors: Tal Eisenberg Source Type: research