Journal of Cell Biology最新文献_第7页

StableMARK-decorated microtubules in cells have expanded lattices. 细胞中经 StableMARK 装饰的微管具有扩展的晶格。

IF 7.8 1区生物学

Journal of Cell Biology Pub Date : 2024-10-10 DOI: 10.1083/jcb.202206143

Leanne de Jager,Klara I Jansen,Robin Hoogebeen,Anna Akhmanova,Lukas C Kapitein,Friedrich Förster,Stuart C Howes

{"title":"StableMARK-decorated microtubules in cells have expanded lattices.","authors":"Leanne de Jager,Klara I Jansen,Robin Hoogebeen,Anna Akhmanova,Lukas C Kapitein,Friedrich Förster,Stuart C Howes","doi":"10.1083/jcb.202206143","DOIUrl":"https://doi.org/10.1083/jcb.202206143","url":null,"abstract":"Microtubules are crucial in cells and are regulated by various mechanisms like posttranslational modifications, microtubule-associated proteins, and tubulin isoforms. Recently, the conformation of the microtubule lattice has also emerged as a potential regulatory factor, but it has remained unclear to what extent different lattices co-exist within the cell. Using cryo-electron tomography, we find that, while most microtubules have a compacted lattice (∼41 Å monomer spacing), approximately a quarter of the microtubules displayed more expanded lattice spacings. The addition of the microtubule-stabilizing agent Taxol increased the lattice spacing of all microtubules, consistent with results on reconstituted microtubules. Furthermore, correlative cryo-light and electron microscopy revealed that the stable subset of microtubules labeled by StableMARK, a marker for stable microtubules, predominantly displayed a more expanded lattice spacing (∼41.9 Å), further suggesting a close connection between lattice expansion and microtubule stability. The coexistence of different lattices and their correlation with stability implicate lattice spacing as an important factor in establishing specific microtubule subsets.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"124 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142436174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

T cells use focal adhesions to pull themselves through confined environments. T 细胞利用病灶粘附力使自己穿过封闭的环境。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-10-07 Epub Date: 2024-06-18 DOI: 10.1083/jcb.202310067

Alexia Caillier, David Oleksyn, Deborah J Fowell, Jim Miller, Patrick W Oakes

{"title":"T cells use focal adhesions to pull themselves through confined environments.","authors":"Alexia Caillier, David Oleksyn, Deborah J Fowell, Jim Miller, Patrick W Oakes","doi":"10.1083/jcb.202310067","DOIUrl":"10.1083/jcb.202310067","url":null,"abstract":"Immune cells are highly dynamic and able to migrate through environments with diverse biochemical and mechanical compositions. Their migration has classically been defined as amoeboid under the assumption that it is integrin independent. Here, we show that activated primary Th1 T cells require both confinement and extracellular matrix proteins to migrate efficiently. This migration is mediated through small and dynamic focal adhesions that are composed of the same proteins associated with canonical mesenchymal cell focal adhesions, such as integrins, talin, and vinculin. These focal adhesions, furthermore, localize to sites of contractile traction stresses, enabling T cells to pull themselves through confined spaces. Finally, we show that Th1 T cells preferentially follow tracks of other T cells, suggesting that these adhesions modify the extracellular matrix to provide additional environmental guidance cues. These results demonstrate not only that the boundaries between amoeboid and mesenchymal migration modes are ambiguous, but that integrin-mediated focal adhesions play a key role in T cell motility.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 10","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419273","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

Calorie restriction activates a gastric Notch-FOXO1 pathway to expand ghrelin cells. 卡路里限制会激活胃 Notch-FOXO1 通路，从而扩大胃泌素细胞。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-10-07 Epub Date: 2024-07-03 DOI: 10.1083/jcb.202305093

Wendy M McKimpson, Sophia Spiegel, Maria Mukhanova, Michael Kraakman, Wen Du, Takumi Kitamoto, Junjie Yu, Zhaobin Deng, Utpal Pajvani, Domenico Accili

{"title":"Calorie restriction activates a gastric Notch-FOXO1 pathway to expand ghrelin cells.","authors":"Wendy M McKimpson, Sophia Spiegel, Maria Mukhanova, Michael Kraakman, Wen Du, Takumi Kitamoto, Junjie Yu, Zhaobin Deng, Utpal Pajvani, Domenico Accili","doi":"10.1083/jcb.202305093","DOIUrl":"10.1083/jcb.202305093","url":null,"abstract":"Calorie restriction increases lifespan. Among the tissue-specific protective effects of calorie restriction, the impact on the gastrointestinal tract remains unclear. We report increased numbers of chromogranin A-positive (+), including orexigenic ghrelin+ cells, in the stomach of calorie-restricted mice. This effect was accompanied by increased Notch target Hes1 and Notch ligand Jag1 and was reversed by blocking Notch with DAPT, a gamma-secretase inhibitor. Primary cultures and genetically modified reporter mice show that increased endocrine cell abundance is due to altered Lgr5+ stem and Neurog3+ endocrine progenitor cell proliferation. Different from the intestine, calorie restriction decreased gastric Lgr5+ stem cells, while increasing a FOXO1/Neurog3+ subpopulation of endocrine progenitors in a Notch-dependent manner. Further, activation of FOXO1 was sufficient to promote endocrine cell differentiation independent of Notch. The Notch inhibitor PF-03084014 or ghrelin receptor antagonist GHRP-6 reversed the phenotypic effects of calorie restriction in mice. Tirzepatide additionally expanded ghrelin+ cells in mice. In summary, calorie restriction promotes Notch-dependent, FOXO1-regulated gastric endocrine cell differentiation.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 10","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11222742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492064","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

UBAP2L contributes to formation of P-bodies and modulates their association with stress granules. UBAP2L 有助于 P 型体的形成，并能调节它们与应激颗粒的结合。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-10-07 Epub Date: 2024-07-15 DOI: 10.1083/jcb.202307146

Claire L Riggs, Nancy Kedersha, Misheel Amarsanaa, Safiyah Noor Zubair, Pavel Ivanov, Paul Anderson

{"title":"UBAP2L contributes to formation of P-bodies and modulates their association with stress granules.","authors":"Claire L Riggs, Nancy Kedersha, Misheel Amarsanaa, Safiyah Noor Zubair, Pavel Ivanov, Paul Anderson","doi":"10.1083/jcb.202307146","DOIUrl":"10.1083/jcb.202307146","url":null,"abstract":"Stress triggers the formation of two distinct cytoplasmic biomolecular condensates: stress granules (SGs) and processing bodies (PBs), both of which may contribute to stress-responsive translation regulation. Though PBs can be present constitutively, stress can increase their number and size and lead to their interaction with stress-induced SGs. The mechanism of such interaction, however, is largely unknown. Formation of canonical SGs requires the RNA binding protein Ubiquitin-Associated Protein 2-Like (UBAP2L), which is a central SG node protein in the RNA-protein interaction network of SGs and PBs. UBAP2L binds to the essential SG and PB proteins G3BP and DDX6, respectively. Research on UBAP2L has mostly focused on its role in SGs, but not its connection to PBs. We find that UBAP2L is not solely an SG protein but also localizes to PBs in certain conditions, contributes to PB biogenesis and SG-PB interactions, and can nucleate hybrid granules containing SG and PB components in cells. These findings inform a new model for SG and PB formation in the context of UBAP2L's role.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 10","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11248227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616524","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

Dynamic interaction of REEP5-MFN1/2 enables mitochondrial hitchhiking on tubular ER. REEP5-MFN1/2 的动态相互作用使线粒体能够在管状 ER 上搭便车。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-10-07 Epub Date: 2024-08-12 DOI: 10.1083/jcb.202304031

Shue Chen, Yang Sun, Yuling Qin, Lan Yang, Zhenhua Hao, Zhihao Xu, Mikael Björklund, Wei Liu, Zhi Hong

{"title":"Dynamic interaction of REEP5-MFN1/2 enables mitochondrial hitchhiking on tubular ER.","authors":"Shue Chen, Yang Sun, Yuling Qin, Lan Yang, Zhenhua Hao, Zhihao Xu, Mikael Björklund, Wei Liu, Zhi Hong","doi":"10.1083/jcb.202304031","DOIUrl":"10.1083/jcb.202304031","url":null,"abstract":"Mitochondrial functions can be regulated by membrane contact sites with the endoplasmic reticulum (ER). These mitochondria-ER contact sites (MERCs) are functionally heterogeneous and maintained by various tethers. Here, we found that REEP5, an ER tubule-shaping protein, interacts with Mitofusins 1/2 to mediate mitochondrial distribution throughout the cytosol by a new transport mechanism, mitochondrial \"hitchhiking\" with tubular ER on microtubules. REEP5 depletion led to reduced tethering and increased perinuclear localization of mitochondria. Conversely, increasing REEP5 expression facilitated mitochondrial distribution throughout the cytoplasm. Rapamycin-induced irreversible REEP5-MFN1/2 interaction led to mitochondrial hyperfusion, implying that the dynamic release of mitochondria from tethering is necessary for normal mitochondrial distribution and dynamics. Functionally, disruption of MFN2-REEP5 interaction dynamics by forced dimerization or silencing REEP5 modulated the production of mitochondrial reactive oxygen species (ROS). Overall, our results indicate that dynamic REEP5-MFN1/2 interaction mediates cytosolic distribution and connectivity of the mitochondrial network by \"hitchhiking\" and this process regulates mitochondrial ROS, which is vital for multiple physiological functions.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 10","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11318672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916809","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 force-sensitive mutation reveals a non-canonical role for dynein in anaphase progression. 力敏感突变揭示了dynein在无丝分裂进程中的非典型作用。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-10-07 Epub Date: 2024-07-01 DOI: 10.1083/jcb.202310022

David Salvador-Garcia, Li Jin, Andrew Hensley, Mert Gölcük, Emmanuel Gallaud, Sami Chaaban, Fillip Port, Alessio Vagnoni, Vicente José Planelles-Herrero, Mark A McClintock, Emmanuel Derivery, Andrew P Carter, Régis Giet, Mert Gür, Ahmet Yildiz, Simon L Bullock

{"title":"A force-sensitive mutation reveals a non-canonical role for dynein in anaphase progression.","authors":"David Salvador-Garcia, Li Jin, Andrew Hensley, Mert Gölcük, Emmanuel Gallaud, Sami Chaaban, Fillip Port, Alessio Vagnoni, Vicente José Planelles-Herrero, Mark A McClintock, Emmanuel Derivery, Andrew P Carter, Régis Giet, Mert Gür, Ahmet Yildiz, Simon L Bullock","doi":"10.1083/jcb.202310022","DOIUrl":"10.1083/jcb.202310022","url":null,"abstract":"The diverse roles of the dynein motor in shaping microtubule networks and cargo transport complicate in vivo analysis of its functions significantly. To address this issue, we have generated a series of missense mutations in Drosophila Dynein heavy chain. We show that mutations associated with human neurological disease cause a range of defects, including impaired cargo trafficking in neurons. We also describe a novel microtubule-binding domain mutation that specifically blocks the metaphase-anaphase transition during mitosis in the embryo. This effect is independent from dynein's canonical role in silencing the spindle assembly checkpoint. Optical trapping of purified dynein complexes reveals that this mutation only compromises motor performance under load, a finding rationalized by the results of all-atom molecular dynamics simulations. We propose that dynein has a novel function in anaphase progression that depends on it operating in a specific load regime. More broadly, our work illustrates how in vivo functions of motors can be dissected by manipulating their mechanical properties.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 10","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141468236","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

De novo lipid synthesis and polarized prenylation drive cell invasion through basement membrane. 新的脂质合成和极化的前酰化推动细胞侵入基底膜。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-10-07 Epub Date: 2024-07-15 DOI: 10.1083/jcb.202402035

Kieop Park, Aastha Garde, Siddharthan B Thendral, Adam W J Soh, Qiuyi Chi, David R Sherwood

{"title":"De novo lipid synthesis and polarized prenylation drive cell invasion through basement membrane.","authors":"Kieop Park, Aastha Garde, Siddharthan B Thendral, Adam W J Soh, Qiuyi Chi, David R Sherwood","doi":"10.1083/jcb.202402035","DOIUrl":"10.1083/jcb.202402035","url":null,"abstract":"To breach the basement membrane, cells in development and cancer use large, transient, specialized lipid-rich membrane protrusions. Using live imaging, endogenous protein tagging, and cell-specific RNAi during Caenorhabditis elegans anchor cell (AC) invasion, we demonstrate that the lipogenic SREBP transcription factor SBP-1 drives the expression of the fatty acid synthesis enzymes POD-2 and FASN-1 prior to invasion. We show that phospholipid-producing LPIN-1 and sphingomyelin synthase SMS-1, which use fatty acids as substrates, produce lysosome stores that build the AC's invasive protrusion, and that SMS-1 also promotes protrusion localization of the lipid raft partitioning ZMP-1 matrix metalloproteinase. Finally, we discover that HMG-CoA reductase HMGR-1, which generates isoprenoids for prenylation, localizes to the ER and enriches in peroxisomes at the AC invasive front, and that the final transmembrane prenylation enzyme, ICMT-1, localizes to endoplasmic reticulum exit sites that dynamically polarize to deliver prenylated GTPases for protrusion formation. Together, these results reveal a collaboration between lipogenesis and a polarized lipid prenylation system that drives invasive protrusion formation.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 10","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11248228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616523","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

Centrosome-organized plasma membrane infoldings linked to growth of a cortical actin domain. 中心体组织的质膜内折与皮质肌动蛋白结构域的生长有关。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-10-07 Epub Date: 2024-06-27 DOI: 10.1083/jcb.202403115

Rebecca Tam, Tony J C Harris

{"title":"Centrosome-organized plasma membrane infoldings linked to growth of a cortical actin domain.","authors":"Rebecca Tam, Tony J C Harris","doi":"10.1083/jcb.202403115","DOIUrl":"10.1083/jcb.202403115","url":null,"abstract":"Regulated cell shape change requires the induction of cortical cytoskeletal domains. Often, local changes to plasma membrane (PM) topography are involved. Centrosomes organize cortical domains and can affect PM topography by locally pulling the PM inward. Are these centrosome effects coupled? At the syncytial Drosophila embryo cortex, centrosome-induced actin caps grow into dome-like compartments for mitoses. We found the nascent cap to be a collection of PM folds and tubules formed over the astral centrosomal MT array. The localized infoldings require centrosome and dynein activities, and myosin-based surface tension prevents them elsewhere. Centrosome-engaged PM infoldings become specifically enriched with an Arp2/3 induction pathway. Arp2/3 actin network growth between the infoldings counterbalances centrosomal pulling forces and disperses the folds for actin cap expansion. Abnormal domain topography with either centrosome or Arp2/3 disruption correlates with decreased exocytic vesicle association. Together, our data implicate centrosome-organized PM infoldings in coordinating Arp2/3 network growth and exocytosis for cortical domain assembly.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 10","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11215285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141457101","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 genome-wide screen links peroxisome regulation with Wnt signaling through RNF146 and TNKS/2. 一项全基因组筛选通过 RNF146 和 TNKS/2 将过氧物酶体调控与 Wnt 信号传导联系起来。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-10-07 Epub Date: 2024-07-05 DOI: 10.1083/jcb.202312069

Jonathan T Vu, Katherine U Tavasoli, Connor J Sheedy, Soham P Chowdhury, Lori Mandjikian, Julien Bacal, Meghan A Morrissey, Chris D Richardson, Brooke M Gardner

{"title":"A genome-wide screen links peroxisome regulation with Wnt signaling through RNF146 and TNKS/2.","authors":"Jonathan T Vu, Katherine U Tavasoli, Connor J Sheedy, Soham P Chowdhury, Lori Mandjikian, Julien Bacal, Meghan A Morrissey, Chris D Richardson, Brooke M Gardner","doi":"10.1083/jcb.202312069","DOIUrl":"10.1083/jcb.202312069","url":null,"abstract":"Peroxisomes are membrane-bound organelles harboring metabolic enzymes. In humans, peroxisomes are required for normal development, yet the genes regulating peroxisome function remain unclear. We performed a genome-wide CRISPRi screen to identify novel factors involved in peroxisomal homeostasis. We found that inhibition of RNF146, an E3 ligase activated by poly(ADP-ribose), reduced the import of proteins into peroxisomes. RNF146-mediated loss of peroxisome import depended on the stabilization and activity of the poly(ADP-ribose) polymerases TNKS and TNKS2, which bind the peroxisomal membrane protein PEX14. We propose that RNF146 and TNKS/2 regulate peroxisome import efficiency by PARsylation of proteins at the peroxisome membrane. Interestingly, we found that the loss of peroxisomes increased TNKS/2 and RNF146-dependent degradation of non-peroxisomal substrates, including the β-catenin destruction complex component AXIN1, which was sufficient to alter the amplitude of β-catenin transcription. Together, these observations not only suggest previously undescribed roles for RNF146 in peroxisomal regulation but also a novel role in bridging peroxisome function with Wnt/β-catenin signaling during development.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 10","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11223164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534524","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

AMPK activation induces RALDH+ tolerogenic dendritic cells by rewiring glucose and lipid metabolism. AMPK 激活可通过重构葡萄糖和脂质代谢诱导 RALDH+耐受性树突状细胞。

IF 7.4 1区生物学

Journal of Cell Biology Pub Date : 2024-10-07 Epub Date: 2024-08-08 DOI: 10.1083/jcb.202401024

Eline C Brombacher, Thiago A Patente, Alwin J van der Ham, Tijmen J A Moll, Frank Otto, Fenne W M Verheijen, Esther A Zaal, Arnoud H de Ru, Rayman T N Tjokrodirijo, Celia R Berkers, Peter A van Veelen, Bruno Guigas, Bart Everts

{"title":"AMPK activation induces RALDH+ tolerogenic dendritic cells by rewiring glucose and lipid metabolism.","authors":"Eline C Brombacher, Thiago A Patente, Alwin J van der Ham, Tijmen J A Moll, Frank Otto, Fenne W M Verheijen, Esther A Zaal, Arnoud H de Ru, Rayman T N Tjokrodirijo, Celia R Berkers, Peter A van Veelen, Bruno Guigas, Bart Everts","doi":"10.1083/jcb.202401024","DOIUrl":"10.1083/jcb.202401024","url":null,"abstract":"Dendritic cell (DC) activation and function are underpinned by profound changes in cellular metabolism. Several studies indicate that the ability of DCs to promote tolerance is dependent on catabolic metabolism. Yet the contribution of AMP-activated kinase (AMPK), a central energy sensor promoting catabolism, to DC tolerogenicity remains unknown. Here, we show that AMPK activation renders human monocyte-derived DCs tolerogenic as evidenced by an enhanced ability to drive differentiation of regulatory T cells, a process dependent on increased RALDH activity. This is accompanied by several metabolic changes, including increased breakdown of glycerophospholipids, enhanced mitochondrial fission-dependent fatty acid oxidation, and upregulated glucose catabolism. This metabolic rewiring is functionally important as we found interference with these metabolic processes to reduce to various degrees AMPK-induced RALDH activity as well as the tolerogenic capacity of moDCs. Altogether, our findings reveal a key role for AMPK signaling in shaping DC tolerogenicity and suggest AMPK as a target to direct DC-driven tolerogenic responses in therapeutic settings.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"223 10","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11310580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901861","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