PLoS Biology最新文献_第9页

An adhesion signaling axis involving Dystroglycan, β1-Integrin, and Cas adaptor proteins regulates the establishment of the cortical glial scaffold. 涉及Dystroglycon、β1-整合素和Cas衔接蛋白的粘附信号轴调节皮层神经胶质支架的建立。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2023-08-04 eCollection Date: 2023-08-01 DOI: 10.1371/journal.pbio.3002212

Wenny Wong, Jason A Estep, Alyssa M Treptow, Niloofar Rajabli, Jennifer N Jahncke, Teresa Ubina, Kevin M Wright, Martin M Riccomagno

{"title":"An adhesion signaling axis involving Dystroglycan, β1-Integrin, and Cas adaptor proteins regulates the establishment of the cortical glial scaffold.","authors":"Wenny Wong, Jason A Estep, Alyssa M Treptow, Niloofar Rajabli, Jennifer N Jahncke, Teresa Ubina, Kevin M Wright, Martin M Riccomagno","doi":"10.1371/journal.pbio.3002212","DOIUrl":"10.1371/journal.pbio.3002212","url":null,"abstract":"The mature mammalian cortex is composed of 6 architecturally and functionally distinct layers. Two key steps in the assembly of this layered structure are the initial establishment of the glial scaffold and the subsequent migration of postmitotic neurons to their final position. These processes involve the precise and timely regulation of adhesion and detachment of neural cells from their substrates. Although much is known about the roles of adhesive substrates during neuronal migration and the formation of the glial scaffold, less is understood about how these signals are interpreted and integrated within these neural cells. Here, we provide in vivo evidence that Cas proteins, a family of cytoplasmic adaptors, serve a functional and redundant role during cortical lamination. Cas triple conditional knock-out (Cas TcKO) mice display severe cortical phenotypes that feature cobblestone malformations. Molecular epistasis and genetic experiments suggest that Cas proteins act downstream of transmembrane Dystroglycan and β1-Integrin in a radial glial cell-autonomous manner. Overall, these data establish a new and essential role for Cas adaptor proteins during the formation of cortical circuits and reveal a signaling axis controlling cortical scaffold formation.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"21 8","pages":"e3002212"},"PeriodicalIF":9.8,"publicationDate":"2023-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10431685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10009595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FBXO7/ntc and USP30 antagonistically set the ubiquitination threshold for basal mitophagy and provide a target for Pink1 phosphorylation in vivo. FBXO7/ntc和USP30拮抗地设定了基础有丝分裂的泛素化阈值，并为体内Pink1磷酸化提供了目标。

IF 7.8 1区生物学

PLoS Biology Pub Date : 2023-08-03 eCollection Date: 2023-08-01 DOI: 10.1371/journal.pbio.3002244

Alvaro Sanchez-Martinez, Aitor Martinez, Alexander J Whitworth

{"title":"FBXO7/ntc and USP30 antagonistically set the ubiquitination threshold for basal mitophagy and provide a target for Pink1 phosphorylation in vivo.","authors":"Alvaro Sanchez-Martinez, Aitor Martinez, Alexander J Whitworth","doi":"10.1371/journal.pbio.3002244","DOIUrl":"10.1371/journal.pbio.3002244","url":null,"abstract":"Functional analyses of genes linked to heritable forms of Parkinson's disease (PD) have revealed fundamental insights into the biological processes underpinning pathogenic mechanisms. Mutations in PARK15/FBXO7 cause autosomal recessive PD and FBXO7 has been shown to regulate mitochondrial homeostasis. We investigated the extent to which FBXO7 and its Drosophila orthologue, ntc, share functional homology and explored its role in mitophagy in vivo. We show that ntc mutants partially phenocopy Pink1 and parkin mutants and ntc overexpression supresses parkin phenotypes. Furthermore, ntc can modulate basal mitophagy in a Pink1- and parkin-independent manner by promoting the ubiquitination of mitochondrial proteins, a mechanism that is opposed by the deubiquitinase USP30. This basal ubiquitination serves as the substrate for Pink1-mediated phosphorylation that triggers stress-induced mitophagy. We propose that FBXO7/ntc works in equilibrium with USP30 to provide a checkpoint for mitochondrial quality control in basal conditions in vivo and presents a new avenue for therapeutic approaches.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"21 8","pages":"e3002244"},"PeriodicalIF":7.8,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10427020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10365459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A previously unrecognized superfamily of macro-conotoxins includes an inhibitor of the sensory neuron calcium channel Cav2.3. 一个以前未被识别的大锥虫毒素超家族包括感觉神经元钙通道Cav2.3抑制剂。

IF 7.8 1区生物学

PLoS Biology Pub Date : 2023-08-03 eCollection Date: 2023-08-01 DOI: 10.1371/journal.pbio.3002217

Celeste M Hackney, Paula Flórez Salcedo, Emilie Mueller, Thomas Lund Koch, Lau D Kjelgaard, Maren Watkins, Linda G Zachariassen, Pernille Sønderby Tuelung, Jeffrey R McArthur, David J Adams, Anders S Kristensen, Baldomero Olivera, Rocio K Finol-Urdaneta, Helena Safavi-Hemami, Jens Preben Morth, Lars Ellgaard

{"title":"A previously unrecognized superfamily of macro-conotoxins includes an inhibitor of the sensory neuron calcium channel Cav2.3.","authors":"Celeste M Hackney, Paula Flórez Salcedo, Emilie Mueller, Thomas Lund Koch, Lau D Kjelgaard, Maren Watkins, Linda G Zachariassen, Pernille Sønderby Tuelung, Jeffrey R McArthur, David J Adams, Anders S Kristensen, Baldomero Olivera, Rocio K Finol-Urdaneta, Helena Safavi-Hemami, Jens Preben Morth, Lars Ellgaard","doi":"10.1371/journal.pbio.3002217","DOIUrl":"10.1371/journal.pbio.3002217","url":null,"abstract":"Animal venom peptides represent valuable compounds for biomedical exploration. The venoms of marine cone snails constitute a particularly rich source of peptide toxins, known as conotoxins. Here, we identify the sequence of an unusually large conotoxin, Mu8.1, which defines a new class of conotoxins evolutionarily related to the well-known con-ikot-ikots and 2 additional conotoxin classes not previously described. The crystal structure of recombinant Mu8.1 displays a saposin-like fold and shows structural similarity with con-ikot-ikot. Functional studies demonstrate that Mu8.1 curtails calcium influx in defined classes of murine somatosensory dorsal root ganglion (DRG) neurons. When tested on a variety of recombinantly expressed voltage-gated ion channels, Mu8.1 displayed the highest potency against the R-type (Cav2.3) calcium channel. Ca2+ signals from Mu8.1-sensitive DRG neurons were also inhibited by SNX-482, a known spider peptide modulator of Cav2.3 and voltage-gated K+ (Kv4) channels. Our findings highlight the potential of Mu8.1 as a molecular tool to identify and study neuronal subclasses expressing Cav2.3. Importantly, this multidisciplinary study showcases the potential of uncovering novel structures and bioactivities within the largely unexplored group of macro-conotoxins.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"21 8","pages":"e3002217"},"PeriodicalIF":7.8,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10437998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10102066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characterization of a novel interaction of the Nup159 nucleoporin with asymmetrically localized spindle pole body proteins and its link with autophagy. Nup159核通道蛋白与不对称定位纺锤极体蛋白的新相互作用及其与自噬的联系的表征。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2023-08-03 eCollection Date: 2023-08-01 DOI: 10.1371/journal.pbio.3002224

Inés García de Oya, Javier Manzano-López, Alejandra Álvarez-Llamas, María de la Paz Vázquez-Aroca, Cristina Cepeda-García, Fernando Monje-Casas

{"title":"Characterization of a novel interaction of the Nup159 nucleoporin with asymmetrically localized spindle pole body proteins and its link with autophagy.","authors":"Inés García de Oya, Javier Manzano-López, Alejandra Álvarez-Llamas, María de la Paz Vázquez-Aroca, Cristina Cepeda-García, Fernando Monje-Casas","doi":"10.1371/journal.pbio.3002224","DOIUrl":"10.1371/journal.pbio.3002224","url":null,"abstract":"Both the spindle microtubule-organizing centers and the nuclear pore complexes (NPCs) are convoluted structures where many signaling pathways converge to coordinate key events during cell division. Interestingly, despite their distinct molecular conformation and overall functions, these structures share common components and collaborate in the regulation of essential processes. We have established a new link between microtubule-organizing centers and nuclear pores in budding yeast by unveiling an interaction between the Bfa1/Bub2 complex, a mitotic exit inhibitor that localizes on the spindle pole bodies, and the Nup159 nucleoporin. Bfa1/Bub2 association with Nup159 is reduced in metaphase to not interfere with proper spindle positioning. However, their interaction is stimulated in anaphase and assists the Nup159-dependent autophagy pathway. The asymmetric localization of Bfa1/Bub2 during mitosis raises the possibility that its interaction with Nup159 could differentially promote Nup159-mediated autophagic processes, which might be relevant for the maintenance of the replicative lifespan.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"21 8","pages":"e3002224"},"PeriodicalIF":9.8,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10437821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10102490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gene amplifications cause high-level resistance against albicidin in gram-negative bacteria. 基因扩增导致革兰氏阴性菌对白杆菌素产生高水平耐药性。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2023-08-01 DOI: 10.1371/journal.pbio.3002186

Mareike Saathoff, Simone Kosol, Torsten Semmler, Karsten Tedin, Nicole Dimos, Johannes Kupke, Maria Seidel, Fereshteh Ghazisaeedi, Micela Condor Jonske, Silver A Wolf, Benno Kuropka, Wojciech Czyszczoń, Dmitry Ghilarov, Stefan Grätz, Jonathan G Heddle, Bernhard Loll, Roderich D Süssmuth, Marcus Fulde

{"title":"Gene amplifications cause high-level resistance against albicidin in gram-negative bacteria.","authors":"Mareike Saathoff, Simone Kosol, Torsten Semmler, Karsten Tedin, Nicole Dimos, Johannes Kupke, Maria Seidel, Fereshteh Ghazisaeedi, Micela Condor Jonske, Silver A Wolf, Benno Kuropka, Wojciech Czyszczoń, Dmitry Ghilarov, Stefan Grätz, Jonathan G Heddle, Bernhard Loll, Roderich D Süssmuth, Marcus Fulde","doi":"10.1371/journal.pbio.3002186","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002186","url":null,"abstract":"Antibiotic resistance is a continuously increasing concern for public healthcare. Understanding resistance mechanisms and their emergence is crucial for the development of new antibiotics and their effective use. The peptide antibiotic albicidin is such a promising candidate that, as a gyrase poison, shows bactericidal activity against a wide range of gram-positive and gram-negative bacteria. Here, we report the discovery of a gene amplification-based mechanism that imparts an up to 1000-fold increase in resistance levels against albicidin. RNA sequencing and proteomics data show that this novel mechanism protects Salmonella Typhimurium and Escherichia coli by increasing the copy number of STM3175 (YgiV), a transcription regulator with a GyrI-like small molecule binding domain that traps albicidin with high affinity. X-ray crystallography and molecular docking reveal a new conserved motif in the binding groove of the GyrI-like domain that can interact with aromatic building blocks of albicidin. Phylogenetic studies suggest that this resistance mechanism is ubiquitous in gram-negative bacteria, and our experiments confirm that STM3175 homologs can confer resistance in pathogens such as Vibrio vulnificus and Pseudomonas aeruginosa.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"21 8","pages":"e3002186"},"PeriodicalIF":9.8,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10414762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10358340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Towards a post-pandemic future for global pathogen genome sequencing. 迈向大流行后全球病原体基因组测序的未来。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2023-08-01 DOI: 10.1371/journal.pbio.3002225

Jason T Ladner, Jason W Sahl

引用次数: 1

Pseudomonas aeruginosa type IV pili actively induce mucus contraction to form biofilms in tissue-engineered human airways. 铜绿假单胞菌IV型菌毛在组织工程人体气道中积极诱导粘液收缩形成生物膜。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2023-08-01 DOI: 10.1371/journal.pbio.3002209

Tamara Rossy, Tania Distler, Lucas A Meirelles, Joern Pezoldt, Jaemin Kim, Lorenzo Talà, Nikolaos Bouklas, Bart Deplancke, Alexandre Persat

{"title":"Pseudomonas aeruginosa type IV pili actively induce mucus contraction to form biofilms in tissue-engineered human airways.","authors":"Tamara Rossy, Tania Distler, Lucas A Meirelles, Joern Pezoldt, Jaemin Kim, Lorenzo Talà, Nikolaos Bouklas, Bart Deplancke, Alexandre Persat","doi":"10.1371/journal.pbio.3002209","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002209","url":null,"abstract":"The opportunistic pathogen Pseudomonas aeruginosa causes antibiotic-recalcitrant pneumonia by forming biofilms in the respiratory tract. Despite extensive in vitro experimentation, how P. aeruginosa forms biofilms at the airway mucosa is unresolved. To investigate the process of biofilm formation in realistic conditions, we developed AirGels: 3D, optically accessible tissue-engineered human lung models that emulate the airway mucosal environment. AirGels recapitulate important factors that mediate host-pathogen interactions including mucus secretion, flow and air-liquid interface (ALI), while accommodating high-resolution live microscopy. With AirGels, we investigated the contributions of mucus to P. aeruginosa biofilm biogenesis in in vivo-like conditions. We found that P. aeruginosa forms mucus-associated biofilms within hours by contracting luminal mucus early during colonization. Mucus contractions facilitate aggregation, thereby nucleating biofilms. We show that P. aeruginosa actively contracts mucus using retractile filaments called type IV pili. Our results therefore suggest that, while protecting epithelia, mucus constitutes a breeding ground for biofilms.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"21 8","pages":"e3002209"},"PeriodicalIF":9.8,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10393179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9932697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Lmo4 synergizes with Fezf2 to promote direct in vivo reprogramming of upper layer cortical neurons and cortical glia towards deep-layer neuron identities. Lmo4与Fezf2协同作用，直接在体内促进上层皮质神经元和皮层胶质向深层神经元身份的重编程。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2023-08-01 DOI: 10.1371/journal.pbio.3002237

Torsten Felske, Chiara Tocco, Sophie Péron, Kawssar Harb, Christian Alfano, Chiara Galante, Benedikt Berninger, Michèle Studer

{"title":"Lmo4 synergizes with Fezf2 to promote direct in vivo reprogramming of upper layer cortical neurons and cortical glia towards deep-layer neuron identities.","authors":"Torsten Felske, Chiara Tocco, Sophie Péron, Kawssar Harb, Christian Alfano, Chiara Galante, Benedikt Berninger, Michèle Studer","doi":"10.1371/journal.pbio.3002237","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002237","url":null,"abstract":"In vivo direct neuronal reprogramming relies on the implementation of an exogenous transcriptional program allowing to achieve conversion of a particular neuronal or glial cell type towards a new identity. The transcription factor (TF) Fezf2 is known for its role in neuronal subtype specification of deep-layer (DL) subcortical projection neurons. High ectopic Fezf2 expression in mice can convert both upper-layer (UL) and striatal projection neurons into a corticofugal fate, even if at low efficiency. In this study, we show that Fezf2 synergizes with the nuclear co-adaptor Lmo4 to further enhance reprogramming of UL cortical pyramidal neurons into DL corticofugal neurons, at both embryonic and early postnatal stages. Reprogrammed neurons express DL molecular markers and project toward subcerebral targets, including thalamus, cerebral peduncle (CP), and spinal cord (SC). We also show that co-expression of Fezf2 with the reprogramming factors Neurog2 and Bcl2 in early postnatal mouse glia promotes glia-to-neuron conversion with partial hallmarks of DL neurons and with Lmo4 promoting further morphological complexity. These data support a novel role for Lmo4 in synergizing with Fezf2 during direct lineage conversion in vivo.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"21 8","pages":"e3002237"},"PeriodicalIF":9.8,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10409279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10002971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Music can be reconstructed from human auditory cortex activity using nonlinear decoding models. 利用非线性解码模型可以从人类听觉皮层的活动中重构音乐。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2023-08-01 DOI: 10.1371/journal.pbio.3002176

Ludovic Bellier, Anaïs Llorens, Déborah Marciano, Aysegul Gunduz, Gerwin Schalk, Peter Brunner, Robert T Knight

{"title":"Music can be reconstructed from human auditory cortex activity using nonlinear decoding models.","authors":"Ludovic Bellier, Anaïs Llorens, Déborah Marciano, Aysegul Gunduz, Gerwin Schalk, Peter Brunner, Robert T Knight","doi":"10.1371/journal.pbio.3002176","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002176","url":null,"abstract":"Music is core to human experience, yet the precise neural dynamics underlying music perception remain unknown. We analyzed a unique intracranial electroencephalography (iEEG) dataset of 29 patients who listened to a Pink Floyd song and applied a stimulus reconstruction approach previously used in the speech domain. We successfully reconstructed a recognizable song from direct neural recordings and quantified the impact of different factors on decoding accuracy. Combining encoding and decoding analyses, we found a right-hemisphere dominance for music perception with a primary role of the superior temporal gyrus (STG), evidenced a new STG subregion tuned to musical rhythm, and defined an anterior-posterior STG organization exhibiting sustained and onset responses to musical elements. Our findings show the feasibility of applying predictive modeling on short datasets acquired in single patients, paving the way for adding musical elements to brain-computer interface (BCI) applications.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"21 8","pages":"e3002176"},"PeriodicalIF":9.8,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10427021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10117653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Leveraging type 1 diabetes human genetic and genomic data in the T1D knowledge portal. 利用T1D知识门户中的1型糖尿病人类遗传和基因组数据。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2023-08-01 DOI: 10.1371/journal.pbio.3002233

Parul Kudtarkar, Maria C Costanzo, Ying Sun, Dongkeun Jang, Ryan Koesterer, Josyf C Mychaleckyj, Uma Nayak, Suna Onengut-Gumuscu, Stephen S Rich, Jason A Flannick, Kyle J Gaulton, Noël P Burtt

引用次数: 1