The Journal of Cell Biology最新文献_第2页

IRE1α recognizes a structural motif in cholera toxin to activate an unfolded protein response. IRE1α 能识别霍乱毒素中的一个结构基团，从而激活未折叠蛋白反应。

The Journal of Cell Biology Pub Date : 2024-04-05 DOI: 10.1083/jcb.202402062

M. S. Simpson, Heidi De Luca, Sarah Cauthorn, P. Luong, N. Udeshi, Tanya Svinkina, Stefanie S. Schmieder, Steve Carr, Michael J. Grey, W. Lencer

引用次数: 0

Presynaptic perspective: Axonal transport defects in neurodevelopmental disorders 突触前视角：神经发育障碍中的轴突运输缺陷

The Journal of Cell Biology Pub Date : 2024-04-03 DOI: 10.1083/jcb.202401145

Gui-Jing Xiong, Zu-Hang Sheng

引用次数: 0

Multifaceted modes of γ-tubulin complex recruitment and microtubule nucleation at mitotic centrosomes 有丝分裂中心体γ-微管复合体募集和微管成核的多方面模式

The Journal of Cell Biology Pub Date : 2023-05-18 DOI: 10.1101/2022.09.23.509043

Zihan Zhu, Isabelle Bécam, Corinne A. Tovey, Eugenie C. Yen, F. Bernard, A. Guichet, Paul T. Conduit

{"title":"Multifaceted modes of γ-tubulin complex recruitment and microtubule nucleation at mitotic centrosomes","authors":"Zihan Zhu, Isabelle Bécam, Corinne A. Tovey, Eugenie C. Yen, F. Bernard, A. Guichet, Paul T. Conduit","doi":"10.1101/2022.09.23.509043","DOIUrl":"https://doi.org/10.1101/2022.09.23.509043","url":null,"abstract":"Microtubule nucleation is mediated by γ-tubulin ring complexes (γ-TuRCs). In most eukaryotes, a GCP4/5/4/6 “core” complex promotes γ-tubulin small complex (γ-TuSC) association to generate cytosolic γ-TuRCs. Unlike γ-TuSCs, however, this core complex is non-essential in various species and absent from budding yeasts. In Drosophila, Spindle defective-2 (Spd-2) and Centrosomin (Cnn) redundantly recruit γ-tubulin complexes to mitotic centrosomes. Here we show that Spd-2 recruits γ-TuRCs formed via the GCP4/5/4/6 core, but that Cnn can recruit γ-TuSCs directly via its well-conserved CM1 domain, similar to its homologues in budding yeast. When centrosomes fail to recruit γ-tubulin complexes, they still nucleate microtubules via the TOG domain protein Mini-spindles (Msps), but these microtubules have different dynamic properties. Our data therefore help explain the dispensability of the GCP4/5/4/6 core and highlight the robustness of centrosomes as microtubule organising centres. They also suggest that the dynamic properties of microtubules are influenced by how they were nucleated.","PeriodicalId":343306,"journal":{"name":"The Journal of Cell Biology","volume":"43 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132144107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PP6 regulation of Aurora A–TPX2 limits NDC80 phosphorylation and mitotic spindle size PP6调控Aurora A-TPX2限制NDC80磷酸化和有丝分裂纺锤体大小

The Journal of Cell Biology Pub Date : 2023-01-18 DOI: 10.1101/2022.05.23.492953

Tomoaki Sobajima, Katarzyna M. Kowalczyk, Stefanos Skylakakis, D. Hayward, Luke J. Fulcher, Colette Neary, Caleb Batley, Samvid Kurlekar, E. Roberts, U. Gruneberg, F. Barr

{"title":"PP6 regulation of Aurora A–TPX2 limits NDC80 phosphorylation and mitotic spindle size","authors":"Tomoaki Sobajima, Katarzyna M. Kowalczyk, Stefanos Skylakakis, D. Hayward, Luke J. Fulcher, Colette Neary, Caleb Batley, Samvid Kurlekar, E. Roberts, U. Gruneberg, F. Barr","doi":"10.1101/2022.05.23.492953","DOIUrl":"https://doi.org/10.1101/2022.05.23.492953","url":null,"abstract":"Amplification of the mitotic kinase Aurora A or loss of its regulator protein phosphatase 6 (PP6) have emerged as drivers of genome instability. Cells lacking PPP6C, the catalytic subunit of PP6, have amplified Aurora A activity and as we show here, enlarged mitotic spindles which fail to hold chromosomes tightly together in anaphase, causing defective nuclear structure. Using functional genomics to shed light on the processes underpinning these changes, we discover synthetic lethality between PPP6C and the kinetochore protein NDC80. We find that NDC80 is phosphorylated on multiple N-terminal sites during spindle formation by Aurora A-TPX2, exclusively at checkpoint-silenced, microtubule-attached kinetochores. NDC80 phosphorylation persists until spindle disassembly in telophase, is increased in PPP6C-knockout cells and, and is Aurora B-independent. An Aurora-phosphorylation-deficient NDC80-9A mutant reduces spindle size and suppresses defective nuclear structure in PPP6C-knockout cells. By regulating NDC80 phosphorylation by Aurora A-TPX2, PP6 plays an important role in mitotic spindle formation and size control, and thus the fidelity of cell division.","PeriodicalId":343306,"journal":{"name":"The Journal of Cell Biology","volume":"11 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115110561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

SIR telomere silencing depends on nuclear envelope lipids and modulates sensitivity to a lysolipid SIR端粒沉默依赖于核膜脂质和调节对溶脂质的敏感性

The Journal of Cell Biology Pub Date : 2023-01-09 DOI: 10.1101/2022.07.08.499406

M. L. Sosa Ponce, Mayrene Horta Remedios, Sarah Moradi-Fard, J. Cobb, V. Zaremberg

{"title":"SIR telomere silencing depends on nuclear envelope lipids and modulates sensitivity to a lysolipid","authors":"M. L. Sosa Ponce, Mayrene Horta Remedios, Sarah Moradi-Fard, J. Cobb, V. Zaremberg","doi":"10.1101/2022.07.08.499406","DOIUrl":"https://doi.org/10.1101/2022.07.08.499406","url":null,"abstract":"The nuclear envelope (NE) is important in maintaining genome organization. The role of lipids in the communication between the NE and telomere silencing was investigated, including how changes in lipid composition impact gene expression and overall nuclear architecture. For this purpose, yeast cells were treated with the non-metabolizable lysophosphatidylcholine analog edelfosine, known to accumulate at the perinuclear endoplasmic reticulum. Edelfosine treatment induced NE deformation and disrupted telomere clustering but not anchoring. In addition, the association of Sir4 at telomeres measured by ChIP decreased. RNA-seq analysis showed altered expression of Sir-dependent genes located at sub-telomeric (0-10 kb) regions, which was consistent with Sir4 dispersion. Transcriptomic analysis revealed that two lipid metabolic circuits were activated in response to edelfosine, one mediated by the membrane sensing transcription factors, Spt23/Mga2, and the other by a transcriptional repressor, Opi1. Activation of these combined transcriptional programs resulted in higher levels of unsaturated fatty acids and the formation of nuclear lipid droplets. Interestingly, cells lacking Sir proteins displayed resistance to unsaturated fatty acids and edelfosine, and this phenotype was connected to Rap1. GRAPHICAL ABSTRACT Summary The nuclear envelope (NE) is important for nuclear organization. This study shows that changes in NE lipid composition from lysolipid treatment decreases Sir4 association with telomeres, their clustering at NE, and triggers lipid-specific transcriptional circuits regulated by membrane-sensing factors.","PeriodicalId":343306,"journal":{"name":"The Journal of Cell Biology","volume":"56 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123525648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The meiotic LINC complex component KASH5 is an activating adaptor for cytoplasmic dynein 减数分裂LINC复合体成分KASH5是细胞质动力蛋白的激活适配器

The Journal of Cell Biology Pub Date : 2022-12-15 DOI: 10.1101/2022.04.13.488131

Kirsten E. L. Garner, A. Salter, C. K. Lau, M. Gurusaran, Cécile Villemant, Elizabeth P. Granger, G. McNee, P. Woodman, O. Davies, B. Burke, V. Allan

{"title":"The meiotic LINC complex component KASH5 is an activating adaptor for cytoplasmic dynein","authors":"Kirsten E. L. Garner, A. Salter, C. K. Lau, M. Gurusaran, Cécile Villemant, Elizabeth P. Granger, G. McNee, P. Woodman, O. Davies, B. Burke, V. Allan","doi":"10.1101/2022.04.13.488131","DOIUrl":"https://doi.org/10.1101/2022.04.13.488131","url":null,"abstract":"Cytoplasmic dynein-driven movement of chromosomes during prophase I of mammalian meiosis is essential for synapsis and genetic exchange. Dynein connects to chromosome telomeres via KASH5 and SUN1 or SUN2, which together span the nuclear envelope. Here, we show that KASH5 promotes dynein motility in vitro, and cytosolic KASH5 inhibits dynein’s interphase functions. KASH5 interacts with either dynein light intermediate chain (DYNC1LI1 or DYNC1LI2) via a conserved helix in the LIC C-terminal, and this region is also needed for dynein’s recruitment to other cellular membranes. KASH5’s N-terminal EF-hands are essential, as the interaction with dynein is disrupted by mutation of key calcium-binding residues, although it is not regulated by cellular calcium levels. Dynein can be recruited to KASH5 at the nuclear envelope independently of dynactin, while LIS1 is essential for dynactin incorporation into the KASH5-dynein complex. Altogether, we show that the trans-membrane protein KASH5 is an activating adaptor for dynein, and shed light on the hierarchy of assembly of KASH5-dynein-dynactin complexes.","PeriodicalId":343306,"journal":{"name":"The Journal of Cell Biology","volume":"62 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128699022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Parallel phospholipid transfer by Vps13 and Atg2 determines autophagosome biogenesis dynamics Vps13和Atg2平行磷脂转移决定自噬体生物发生动力学

The Journal of Cell Biology Pub Date : 2022-11-10 DOI: 10.1101/2022.11.10.516013

Rahel Dabrowski, Susanna Tulli, M. Graef

{"title":"Parallel phospholipid transfer by Vps13 and Atg2 determines autophagosome biogenesis dynamics","authors":"Rahel Dabrowski, Susanna Tulli, M. Graef","doi":"10.1101/2022.11.10.516013","DOIUrl":"https://doi.org/10.1101/2022.11.10.516013","url":null,"abstract":"During autophagy, rapid membrane assembly expands small phagophores into large double-membrane autophagosomes. Theoretical modelling predicts the majority of autophagosomal phospholipids is derived from highly efficient non-vesicular phospholipid transfer (PLT) across phagophore-ER contacts (PERCS). Currently, the phagophore-ER tether Atg2 is the only PLT protein known to drive phagophore expansion in vivo. Here, our quantitative live-cell-imaging analysis reveals poor correlation between duration and size of forming autophagosomes and number of Atg2 molecules at PERCS of starving yeast cells. Strikingly, we find Atg2-mediated PLT is non-rate-limiting for autophagosome biogenesis, because membrane tether and PLT protein Vps13 localizes to the rim and promotes expansion of phagophores in parallel with Atg2. In the absence of Vps13, the number of Atg2 molecules at PERCS determines duration and size of forming autophagosomes with an apparent in vivo transfer rate of ~200 phospholipids per Atg2 molecule and second. We propose conserved PLT proteins cooperate in channeling phospholipids across organelle contact sites for non-rate-limiting membrane assembly during autophagosome biogenesis.","PeriodicalId":343306,"journal":{"name":"The Journal of Cell Biology","volume":"222 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129295225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 10

Lysosomal solute and water transport. 溶酶体溶质和水运输。

IF 7.8

The Journal of Cell Biology Pub Date : 2022-11-07 Epub Date: 2022-10-11 DOI: 10.1083/jcb.202109133

Meiqin Hu, Nan Zhou, Weijie Cai, Haoxing Xu

引用次数: 7

Spatiotemporal control of actomyosin contractility by MRCKβ signaling drives phagocytosis. MRCKβ信号传导对肌动球蛋白收缩性的时空调控驱动吞噬作用。

IF 7.8

The Journal of Cell Biology Pub Date : 2022-11-07 Epub Date: 2022-09-19 DOI: 10.1083/jcb.202012042

Ceniz Zihni, Anastasios Georgiadis, Conor M Ramsden, Elena Sanchez-Heras, Alexis J Haas, Britta Nommiste, Olha Semenyuk, James W B Bainbridge, Peter J Coffey, Alexander J Smith, Robin R Ali, Maria S Balda, Karl Matter

{"title":"Spatiotemporal control of actomyosin contractility by MRCKβ signaling drives phagocytosis.","authors":"Ceniz Zihni, Anastasios Georgiadis, Conor M Ramsden, Elena Sanchez-Heras, Alexis J Haas, Britta Nommiste, Olha Semenyuk, James W B Bainbridge, Peter J Coffey, Alexander J Smith, Robin R Ali, Maria S Balda, Karl Matter","doi":"10.1083/jcb.202012042","DOIUrl":"https://doi.org/10.1083/jcb.202012042","url":null,"abstract":"Phagocytosis requires actin dynamics, but whether actomyosin contractility plays a role in this morphodynamic process is unclear. Here, we show that in the retinal pigment epithelium (RPE), particle binding to Mer Tyrosine Kinase (MerTK), a widely expressed phagocytic receptor, stimulates phosphorylation of the Cdc42 GEF Dbl3, triggering activation of MRCKβ/myosin-II and its coeffector N-WASP, membrane deformation, and cup formation. Continued MRCKβ/myosin-II activity then drives recruitment of a mechanosensing bridge, enabling cytoskeletal force transmission, cup closure, and particle internalization. In vivo, MRCKβ is essential for RPE phagocytosis and retinal integrity. MerTK-independent activation of MRCKβ signaling by a phosphomimetic Dbl3 mutant rescues phagocytosis in retinitis pigmentosa RPE cells lacking functional MerTK. MRCKβ is also required for efficient particle translocation from the cortex into the cell body in Fc receptor-mediated phagocytosis. Thus, conserved MRCKβ signaling at the cortex controls spatiotemporal regulation of actomyosin contractility to guide distinct phases of phagocytosis in the RPE and represents the principle phagocytic effector pathway downstream of MerTK.","PeriodicalId":343306,"journal":{"name":"The Journal of Cell Biology","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2022-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9485704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40366493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Vav independently regulates synaptic growth and plasticity through distinct actin-based processes. Vav通过不同的基于肌动蛋白的过程独立调节突触的生长和可塑性。

IF 7.8

The Journal of Cell Biology Pub Date : 2022-10-03 Epub Date: 2022-08-17 DOI: 10.1083/jcb.202203048

Hyun Gwan Park, Yeongjin David Kim, Eunsang Cho, Ting-Yi Lu, Chi-Kuang Yao, Jihye Lee, Seungbok Lee

{"title":"Vav independently regulates synaptic growth and plasticity through distinct actin-based processes.","authors":"Hyun Gwan Park, Yeongjin David Kim, Eunsang Cho, Ting-Yi Lu, Chi-Kuang Yao, Jihye Lee, Seungbok Lee","doi":"10.1083/jcb.202203048","DOIUrl":"https://doi.org/10.1083/jcb.202203048","url":null,"abstract":"Modulation of presynaptic actin dynamics is fundamental to synaptic growth and functional plasticity; yet the underlying molecular and cellular mechanisms remain largely unknown. At Drosophila NMJs, the presynaptic Rac1-SCAR pathway mediates BMP-induced receptor macropinocytosis to inhibit BMP growth signaling. Here, we show that the Rho-type GEF Vav acts upstream of Rac1 to inhibit synaptic growth through macropinocytosis. We also present evidence that Vav-Rac1-SCAR signaling has additional roles in tetanus-induced synaptic plasticity. Presynaptic inactivation of Vav signaling pathway components, but not regulators of macropinocytosis, impairs post-tetanic potentiation (PTP) and enhances synaptic depression depending on external Ca2+ concentration. Interfering with the Vav-Rac1-SCAR pathway also impairs mobilization of reserve pool (RP) vesicles required for tetanus-induced synaptic plasticity. Finally, treatment with an F-actin-stabilizing drug completely restores RP mobilization and plasticity defects in Vav mutants. We propose that actin-regulatory Vav-Rac1-SCAR signaling independently regulates structural and functional presynaptic plasticity by driving macropinocytosis and RP mobilization, respectively.","PeriodicalId":343306,"journal":{"name":"The Journal of Cell Biology","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2022-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9388202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40620113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4