IF 6.4 1区生物学

eLife Pub Date : 2024-10-31 DOI: 10.7554/eLife.93172

Ewa K Bomba-Warczak, Karen M Velez, Luhan T Zhou, Christelle Guillermier, Seby Edassery, Matthew L Steinhauser, Jeffrey N Savas, Francesca E Duncan

引用次数: 0

Structural basis for molecular assembly of fucoxanthin chlorophyll a/c-binding proteins in a diatom photosystem I supercomplex. 硅藻光合系统 I 超级复合物中的叶绿素 a/c 结合蛋白分子组装的结构基础。

IF 6.4 1区生物学

eLife Pub Date : 2024-10-31 DOI: 10.7554/eLife.99858

Koji Kato, Yoshiki Nakajima, Jian Xing, Minoru Kumazawa, Haruya Ogawa, Jian-Ren Shen, Kentaro Ifuku, Ryo Nagao

{"title":"Structural basis for molecular assembly of fucoxanthin chlorophyll a/c-binding proteins in a diatom photosystem I supercomplex.","authors":"Koji Kato, Yoshiki Nakajima, Jian Xing, Minoru Kumazawa, Haruya Ogawa, Jian-Ren Shen, Kentaro Ifuku, Ryo Nagao","doi":"10.7554/eLife.99858","DOIUrl":"10.7554/eLife.99858","url":null,"abstract":"Photosynthetic organisms exhibit remarkable diversity in their light-harvesting complexes (LHCs). LHCs are associated with photosystem I (PSI), forming a PSI-LHCI supercomplex. The number of LHCI subunits, along with their protein sequences and pigment compositions, has been found to differ greatly among the PSI-LHCI structures. However, the mechanisms by which LHCIs recognize their specific binding sites within the PSI core remain unclear. In this study, we determined the cryo-electron microscopy structure of a PSI supercomplex incorporating fucoxanthin chlorophyll a/c-binding proteins (FCPs), designated as PSI-FCPI, isolated from the diatom Thalassiosira pseudonana CCMP1335. Structural analysis of PSI-FCPI revealed five FCPI subunits associated with a PSI monomer; these subunits were identified as RedCAP, Lhcr3, Lhcq10, Lhcf10, and Lhcq8. Through structural and sequence analyses, we identified specific protein-protein interactions at the interfaces between FCPI and PSI subunits, as well as among FCPI subunits themselves. Comparative structural analyses of PSI-FCPI supercomplexes, combined with phylogenetic analysis of FCPs from T. pseudonana and the diatom Chaetoceros gracilis, underscore the evolutionary conservation of protein motifs crucial for the selective binding of individual FCPI subunits. These findings provide significant insights into the molecular mechanisms underlying the assembly and selective binding of FCPIs in diatoms.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557450","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

Neurons enhance blood-brain barrier function via upregulating claudin-5 and VE-cadherin expression due to glial cell line-derived neurotrophic factor secretion. 神经元通过分泌胶质细胞系源性神经营养因子上调 claudin-5 和 VE-cadherin 的表达，增强血脑屏障功能。

IF 6.4 1区生物学

eLife Pub Date : 2024-10-30 DOI: 10.7554/eLife.96161

Lu Yang, Zijin Lin, Ruijing Mu, Wenhan Wu, Hao Zhi, Xiaodong Liu, Hanyu Yang, Li Liu

{"title":"Neurons enhance blood-brain barrier function via upregulating claudin-5 and VE-cadherin expression due to glial cell line-derived neurotrophic factor secretion.","authors":"Lu Yang, Zijin Lin, Ruijing Mu, Wenhan Wu, Hao Zhi, Xiaodong Liu, Hanyu Yang, Li Liu","doi":"10.7554/eLife.96161","DOIUrl":"10.7554/eLife.96161","url":null,"abstract":"Blood-brain barrier (BBB) prevents neurotoxins from entering central nervous system. We aimed to establish and characterize an in vitro triple co-culture BBB model consisting of brain endothelial cells hCMEC/D3, astrocytoma U251 cells, and neuroblastoma SH-SY5Y cells. Co-culture of SH-SY5Y and U251 cells markedly enhanced claudin-5 and VE-cadherin expression in hCMEC/D3 cells, accompanied by increased transendothelial electrical resistance and decreased permeability. Conditioned medium (CM) from SH-SY5Y cells (S-CM), U251 cells (U-CM), and co-culture of SH-SY5Y and U251 cells (US-CM) also promoted claudin-5 and VE-cadherin expression. Glial cell line-derived neurotrophic factor (GDNF) levels in S-CM and US-CM were significantly higher than CMs from hCMEC/D3 and U-CM. Both GDNF and US-CM upregulated claudin-5 and VE-cadherin expression, which were attenuated by anti-GDNF antibody and GDNF signaling inhibitors. GDNF increased claudin-5 expression via the PI3K/AKT/FOXO1 and MAPK/ERK pathways. Meanwhile, GDNF promoted VE-cadherin expression by activating PI3K/AKT/ETS1 and MAPK/ERK/ETS1 signaling. The roles of GDNF in BBB integrity were validated using brain-specific Gdnf silencing mice. The developed triple co-culture BBB model was successfully applied to predict BBB permeability. In conclusion, neurons enhance BBB integrity by upregulating claudin-5 and VE-cadherin expression through GDNF secretion and established triple co-culture BBB model may be used to predict drugs' BBB permeability.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544385","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

Antibodies get under the skin. 抗体进入皮下

IF 6.4 1区生物学

eLife Pub Date : 2024-10-30 DOI: 10.7554/eLife.104040

Chiara Levra Levron, Gabriele Piacenti, Giacomo Donati

引用次数: 0

PKCδ is an activator of neuronal mitochondrial metabolism that mediates the spacing effect on memory consolidation. PKCδ 是神经元线粒体新陈代谢的激活剂，它介导了记忆巩固的间距效应。

IF 6.4 1区生物学

eLife Pub Date : 2024-10-30 DOI: 10.7554/eLife.92085

Typhaine Comyn, Thomas Preat, Alice Pavlowsky, Pierre-Yves Plaçais

{"title":"PKCδ is an activator of neuronal mitochondrial metabolism that mediates the spacing effect on memory consolidation.","authors":"Typhaine Comyn, Thomas Preat, Alice Pavlowsky, Pierre-Yves Plaçais","doi":"10.7554/eLife.92085","DOIUrl":"10.7554/eLife.92085","url":null,"abstract":"Relevance-based selectivity and high energy cost are two distinct features of long-term memory (LTM) formation that warrant its default inhibition. Spaced repetition of learning is a highly conserved cognitive mechanism that can lift this inhibition. Here, we questioned how the spacing effect integrates experience selection and energy efficiency at the cellular and molecular levels. We showed in Drosophila that spaced training triggers LTM formation by extending over several hours an increased mitochondrial metabolic activity in neurons of the associative memory center, the mushroom bodies (MBs). We found that this effect is mediated by PKCδ, a member of the so-called 'novel PKC' family of enzymes, which uncovers the critical function of PKCδ in neurons as a regulator of mitochondrial metabolism for LTM. Additionally, PKCδ activation and translocation to mitochondria result from LTM-specific dopamine signaling on MB neurons. By bridging experience-dependent neuronal circuit activity with metabolic modulation of memory-encoding neurons, PKCδ signaling binds the cognitive and metabolic constraints underlying LTM formation into a unified gating mechanism.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544386","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

Whole blood transcriptional profiles and the pathogenesis of tuberculous meningitis. 结核性脑膜炎的全血转录谱和发病机制。

IF 6.4 1区生物学

eLife Pub Date : 2024-10-30 DOI: 10.7554/eLife.92344

Hoang Thanh Hai, Le Thanh Hoang Nhat, Trinh Thi Bich Tram, Do Dinh Vinh, Artika P Nath, Joseph Donovan, Nguyen Thi Anh Thu, Dang Van Thanh, Nguyen Duc Bang, Dang Thi Minh Ha, Nguyen Hoan Phu, Ho Dang Trung Nghia, Le Hong Van, Michael Inouye, Guy E Thwaites, Nguyen Thuy Thuong Thuong

{"title":"Whole blood transcriptional profiles and the pathogenesis of tuberculous meningitis.","authors":"Hoang Thanh Hai, Le Thanh Hoang Nhat, Trinh Thi Bich Tram, Do Dinh Vinh, Artika P Nath, Joseph Donovan, Nguyen Thi Anh Thu, Dang Van Thanh, Nguyen Duc Bang, Dang Thi Minh Ha, Nguyen Hoan Phu, Ho Dang Trung Nghia, Le Hong Van, Michael Inouye, Guy E Thwaites, Nguyen Thuy Thuong Thuong","doi":"10.7554/eLife.92344","DOIUrl":"10.7554/eLife.92344","url":null,"abstract":"Mortality and morbidity from tuberculous meningitis (TBM) are common, primarily due to inflammatory response to Mycobacterium tuberculosis infection, yet the underlying mechanisms remain poorly understood. We aimed to uncover genes and pathways associated with TBM pathogenesis and mortality, and determine the best predictors of death, utilizing whole-blood RNA sequencing from 281 Vietnamese adults with TBM, 295 pulmonary tuberculosis (PTB), and 30 healthy controls. Through weighted gene co-expression network analysis, we identified hub genes and pathways linked to TBM severity and mortality, with a consensus analysis revealing distinct patterns between HIV-positive and HIV-negative individuals. We employed multivariate elastic-net Cox regression to select candidate predictors of death, then logistic regression and internal bootstrap validation to choose best predictors. Increased neutrophil activation and decreased T and B cell activation pathways were associated with TBM mortality. Among HIV-positive individuals, mortality associated with increased angiogenesis, while HIV-negative individuals exhibited elevated TNF signaling and impaired extracellular matrix organization. Four hub genes-MCEMP1, NELL2, ZNF354C, and CD4-were strong TBM mortality predictors. These findings indicate that TBM induces a systemic inflammatory response similar to PTB, highlighting critical genes and pathways related to death, offering insights for potential therapeutic targets alongside a novel four-gene biomarker for predicting outcomes.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544398","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

Predicting the sequence-dependent backbone dynamics of intrinsically disordered proteins. 预测内在无序蛋白质的序列依赖性骨架动力学。

IF 6.4 1区生物学

eLife Pub Date : 2024-10-30 DOI: 10.7554/eLife.88958

Sanbo Qin, Huan-Xiang Zhou

引用次数: 0

The zinc transporter Slc30a1 (ZnT1) in macrophages plays a protective role against attenuated Salmonella. 巨噬细胞中的锌转运体 Slc30a1 (ZnT1) 对减毒沙门氏菌具有保护作用。

IF 6.4 1区生物学

eLife Pub Date : 2024-10-30 DOI: 10.7554/eLife.89509

Pinanong Na-Phatthalung, Shumin Sun, Enjun Xie, Jia Wang, Junxia Min, Fudi Wang

{"title":"The zinc transporter Slc30a1 (ZnT1) in macrophages plays a protective role against attenuated Salmonella.","authors":"Pinanong Na-Phatthalung, Shumin Sun, Enjun Xie, Jia Wang, Junxia Min, Fudi Wang","doi":"10.7554/eLife.89509","DOIUrl":"10.7554/eLife.89509","url":null,"abstract":"The zinc transporter Slc30a1 plays an essential role in maintaining cellular zinc homeostasis. Despite this, its functional role in macrophages remains largely unknown. Here, we examine the function of Slc30a1 in host defense using mice models infected with an attenuated stain of Salmonella enterica Typhimurium and primary macrophages infected with the attenuated Salmonella. Bulk transcriptome sequencing in primary macrophages identifies Slc30a1 as a candidate in response to Salmonella infection. Whole-mount immunofluorescence and confocal microscopy imaging of primary macrophage and spleen from Salmonella-infected Slc30a1flag-EGFP mice demonstrate Slc30a1 expression is increased in infected macrophages with localization at the plasma membrane and in the cytosol. Lyz2-Cre-driven Slc30a1 conditional knockout mice (Slc30a1fl/fl;Lyz2-Cre) exhibit increased susceptibility to Salmonella infection compared to control littermates. We demonstrate that Slc30a1-deficient macrophages are defective in intracellular killing, which correlated with reduced activation of nuclear factor kappa B and reduction in nitric oxide (NO) production. Notably, the model exhibits intracellular zinc accumulation, demonstrating that Slc30a1 is required for zinc export. We thus conclude that zinc export enables the efficient NO-mediated antibacterial activity of macrophages to control invading Salmonella.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544389","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

Rab11 suppresses neuronal stress signaling by localizing dual leucine zipper kinase to axon terminals for protein turnover. Rab11通过将双亮氨酸拉链激酶定位到轴突末端以促进蛋白质周转，从而抑制神经元应激信号传导。

IF 6.4 1区生物学

eLife Pub Date : 2024-10-30 DOI: 10.7554/eLife.96592

Seung Mi Kim, Yaw Quagraine, Monika Singh, Jung Hwan Kim

{"title":"Rab11 suppresses neuronal stress signaling by localizing dual leucine zipper kinase to axon terminals for protein turnover.","authors":"Seung Mi Kim, Yaw Quagraine, Monika Singh, Jung Hwan Kim","doi":"10.7554/eLife.96592","DOIUrl":"10.7554/eLife.96592","url":null,"abstract":"Dual leucine zipper kinase (DLK) mediates multiple neuronal stress responses, and its expression levels are constantly suppressed to prevent excessive stress signaling. We found that Wallenda (Wnd), the Drosophila ortholog of DLK, is highly enriched in the axon terminals of Drosophila sensory neurons in vivo and that this subcellular localization is necessary for Highwire-mediated Wnd protein turnover under normal conditions. Our structure-function analysis found that Wnd palmitoylation is essential for its axon terminal localization. Palmitoylation-defective Wnd accumulated in neuronal cell bodies, exhibited dramatically increased protein expression levels, and triggered excessive neuronal stress responses. Defective intracellular transport is implicated in neurodegenerative conditions. Comprehensive dominant-negative Rab protein screening identified Rab11 as an essential factor for Wnd localization in axon terminals. Consequently, Rab11 loss-of-function increased the protein levels of Wnd and induced neuronal stress responses. Inhibiting Wnd activity significantly ameliorated neuronal loss and c-Jun N-terminal kinase signaling triggered by Rab11 loss-of-function. Taken together, these suggest that DLK proteins are constantly transported to axon terminals for protein turnover and a failure of such transport can lead to neuronal loss. Our study demonstrates how subcellular protein localization is coupled to protein turnover for neuronal stress signaling.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544388","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

Spatial transcriptomics of meningeal inflammation reveals inflammatory gene signatures in adjacent brain parenchyma. 脑膜炎症的空间转录组学揭示了邻近脑实质的炎症基因特征。

IF 6.4 1区生物学

eLife Pub Date : 2024-10-30 DOI: 10.7554/eLife.88414

Sachin P Gadani, Saumitra Singh, Sophia Kim, Jingwen Hu, Matthew D Smith, Peter A Calabresi, Pavan Bhargava

{"title":"Spatial transcriptomics of meningeal inflammation reveals inflammatory gene signatures in adjacent brain parenchyma.","authors":"Sachin P Gadani, Saumitra Singh, Sophia Kim, Jingwen Hu, Matthew D Smith, Peter A Calabresi, Pavan Bhargava","doi":"10.7554/eLife.88414","DOIUrl":"10.7554/eLife.88414","url":null,"abstract":"While modern high efficacy disease modifying therapies have revolutionized the treatment of relapsing-remitting multiple sclerosis, they are less effective at controlling progressive forms of the disease. Meningeal inflammation is a recognized risk factor for cortical gray matter pathology which can result in disabling symptoms such as cognitive impairment and depression, but the mechanisms linking meningeal inflammation and gray matter pathology remain unclear. Here, we performed magnetic resonance imaging (MRI)-guided spatial transcriptomics in a mouse model of autoimmune meningeal inflammation to characterize the transcriptional signature in areas of meningeal inflammation and the underlying brain parenchyma. We found broadly increased activity of inflammatory signaling pathways at sites of meningeal inflammation, but only a subset of these pathways active in the adjacent brain parenchyma. Subclustering of regions adjacent to meningeal inflammation revealed the subset of immune programs induced in brain parenchyma, notably complement signaling and antigen processing/presentation. Trajectory gene and gene set modeling analysis confirmed variable penetration of immune signatures originating from meningeal inflammation into the adjacent brain tissue. This work contributes a valuable data resource to the field, provides the first detailed spatial transcriptomic characterization in a model of meningeal inflammation, and highlights several candidate pathways in the pathogenesis of gray matter pathology.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544443","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

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