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Rapid degradation of GRASP55 and GRASP65 reveals their immediate impact on the Golgi structure GRASP55和GRASP65的快速降解揭示了它们对高尔基结构的直接影响
The Journal of Cell Biology Pub Date : 2020-07-07 DOI: 10.1101/2020.07.07.192609
Yijun Zhang, J. Seemann
{"title":"Rapid degradation of GRASP55 and GRASP65 reveals their immediate impact on the Golgi structure","authors":"Yijun Zhang, J. Seemann","doi":"10.1101/2020.07.07.192609","DOIUrl":"https://doi.org/10.1101/2020.07.07.192609","url":null,"abstract":"GRASP65 and GRASP55 have been implicated in stacking of Golgi cisternae and lateral linking of stacks within the Golgi ribbon. However, loss of gene function approaches by RNAi or gene knockout to dissect their respective roles often resulted in conflicting conclusions. Here, we gene-edited GRASP55 and/or GRASP65 with a degron tag in human fibroblasts, allowing for the induced rapid degradation by the proteasome. We show that acute depletion of either GRASP55 or GRASP65 does not affect the Golgi ribbon, while chronic degradation of GRASP55 disrupts lateral connectivity of the Golgi ribbon. Acute double depletion of both GRASPs coincides with the loss of the vesicle tethering proteins GM130, p115 and Golgin-45 from the Golgi and compromises ribbon linking. Furthermore, neither GRASP55 and/or GRASP65 are required for maintaining stacks or de novo assembly of stacked cisternae at the end of mitosis. These results demonstrate that both GRASPs are dispensable for Golgi stacking, but are involved in maintaining the integrity of Golgi ribbon together with GM130 and Golgin-45.","PeriodicalId":343306,"journal":{"name":"The Journal of Cell Biology","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131991420","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: 30
The UPRmt preserves mitochondrial import to extend lifespan UPRmt保留线粒体输入以延长寿命
The Journal of Cell Biology Pub Date : 2020-07-02 DOI: 10.1101/2020.07.01.182980
Nan Xin, Jenni Durieux, Chun-hu Yang, Suzanne C. Wolff, Hyun-Eui Kim, A. Dillin
{"title":"The UPRmt preserves mitochondrial import to extend lifespan","authors":"Nan Xin, Jenni Durieux, Chun-hu Yang, Suzanne C. Wolff, Hyun-Eui Kim, A. Dillin","doi":"10.1101/2020.07.01.182980","DOIUrl":"https://doi.org/10.1101/2020.07.01.182980","url":null,"abstract":"The mitochondrial unfolded protein response (UPRmt) is dedicated to promote mitochondrial proteostasis and is linked to extreme longevity in worms, flies, and mice. The key regulator of this process is the transcription factor, ATFS-1. In the absence of mitochondrial stress, ATFS-1 is transported to the mitochondria and degraded. During conditions of mitochondrial stress, ATFS-1 is excluded from the mitochondria and enters the nucleus to regulate the expression of UPRmt genes. However, there exists a dichotomy in regards to induction of the UPRmt and mitochondrial import. The repair proteins synthesized as a direct result of UPRmt activation must be transported into damaged mitochondria that had previously excluded ATFS-1 due to reduced import efficiency. To address this conundrum, we analyzed the role of the import machinery under conditions where the UPRmt was induced. Using in vitro biochemical assays of mitochondrial import and in vivo analysis of mitochondrial proteins, we surprisingly find that the efficiency of mitochondrial import increases when the UPRmt is activated in an ATFS-1 dependent manner, even though membrane potential is reduced. The import machinery is upregulated at the transcription and translation level, and intact import machinery is essential for UPRmt-mediated increase and lifespan extension. With age, import capacity decreases, and activation of the UPRmt delays this decline and increases longevity. Finally, we find that ATFS-1 has a significantly weaker mitochondrial targeting sequence (MTS), allowing for dynamic subcellular localization during the initial stages of UPRmt activation.","PeriodicalId":343306,"journal":{"name":"The Journal of Cell Biology","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130050841","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: 21
Entosis and apical cell extrusion constitute a tumor-suppressive mechanism downstream of Matriptase 内吞和根尖细胞挤压构成基质酶下游的肿瘤抑制机制
The Journal of Cell Biology Pub Date : 2019-12-09 DOI: 10.1083/jcb.201905190
J. Armistead, J. Hatzold, Anna van Roye, Evelin Fahle, M. Hammerschmidt
{"title":"Entosis and apical cell extrusion constitute a tumor-suppressive mechanism downstream of Matriptase","authors":"J. Armistead, J. Hatzold, Anna van Roye, Evelin Fahle, M. Hammerschmidt","doi":"10.1083/jcb.201905190","DOIUrl":"https://doi.org/10.1083/jcb.201905190","url":null,"abstract":"The type II transmembrane serine protease Matriptase 1 (ST14) is commonly known as an oncogene, yet it also plays an understudied role in suppressing carcinogenesis. This double face is evident in the embryonic epidermis of zebrafish loss-of-function mutants in the cognate Matriptase inhibitor Hai1a (Spint1a). Mutant embryos display epidermal hyperplasia, but also apical cell extrusions, during which extruding outer keratinocytes carry out an entosis-like engulfment and entrainment of underlying basal cells, constituting a tumor-suppressive effect. These counteracting Matriptase effects depend on EGFR and the newly identified mediator phospholipase D (PLD), which promotes both mTORC1-dependent cell proliferation and sphingosine-1-phosphate (S1P)-dependent entosis and apical cell extrusion. Accordingly, hypomorphic hai1a mutants heal spontaneously, while otherwise lethal hai1a amorphs are efficiently rescued upon cotreatment with PLD inhibitors and S1P. Together, our data elucidate the mechanisms underlying the double face of Matriptase function in vivo and reveal the potential use of combinatorial carcinoma treatments when such double-face mechanisms are involved.","PeriodicalId":343306,"journal":{"name":"The Journal of Cell Biology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114480952","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: 6
NCAM regulates temporal specification of neural progenitor cells via profilin2 during corticogenesis 在皮质发生过程中，NCAM通过profilin2调节神经祖细胞的时间特异性
The Journal of Cell Biology Pub Date : 2019-12-09 DOI: 10.1083/jcb.201902164
Rui Huang, De-Juan Yuan, Shao Li, Xue-Song Liang, Yue Gao, Xiaoyan Lan, Hua-min Qin, Yu-Fang Ma, Guang-Yin Xu, M. Schachner, V. Sytnyk, J. Boltze, Quan-Hong Ma, Shen Li
{"title":"NCAM regulates temporal specification of neural progenitor cells via profilin2 during corticogenesis","authors":"Rui Huang, De-Juan Yuan, Shao Li, Xue-Song Liang, Yue Gao, Xiaoyan Lan, Hua-min Qin, Yu-Fang Ma, Guang-Yin Xu, M. Schachner, V. Sytnyk, J. Boltze, Quan-Hong Ma, Shen Li","doi":"10.1083/jcb.201902164","DOIUrl":"https://doi.org/10.1083/jcb.201902164","url":null,"abstract":"The role of NCAM in corticogenesis is incompletely understood. The authors demonstrate that NCAM controls NPC proliferation and fate decision through profilin2-dependent regulation of actin polymerization. This finding sheds new light on NCAM’s functions in neurodevelopmental and mental disorders.","PeriodicalId":343306,"journal":{"name":"The Journal of Cell Biology","volume":"28 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114392243","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: 12
Relief of talin autoinhibition triggers a force-independent association with vinculin talin自身抑制的解除触发了与血管蛋白的力无关的关联
The Journal of Cell Biology Pub Date : 2019-12-05 DOI: 10.1083/jcb.201903134
P. Atherton, Franziska Lausecker, Alexandre F. Carisey, A. Gilmore, D. Critchley, I. Barsukov, C. Ballestrem
{"title":"Relief of talin autoinhibition triggers a force-independent association with vinculin","authors":"P. Atherton, Franziska Lausecker, Alexandre F. Carisey, A. Gilmore, D. Critchley, I. Barsukov, C. Ballestrem","doi":"10.1083/jcb.201903134","DOIUrl":"https://doi.org/10.1083/jcb.201903134","url":null,"abstract":"Talin and vinculin control mechanosensing by linking adhesion receptors to the contractile actin cytoskeleton. Using a mitochondrial targeting system, Atherton et al. elucidate mechanisms regulating conformational changes required for vinculin binding to talin. Such activation mechanisms are not required for either protein to interact with the adhesion regulatory protein paxillin.","PeriodicalId":343306,"journal":{"name":"The Journal of Cell Biology","volume":"49 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132265591","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: 40
An interphase contractile ring reshapes primordial germ cells to allow bulk cytoplasmic remodeling 一个间期收缩环使原始生殖细胞重塑，从而使大量细胞质重塑
The Journal of Cell Biology Pub Date : 2019-12-05 DOI: 10.1083/jcb.201906185
Chelsea Maniscalco, Allison E. Hall, J. Nance
{"title":"An interphase contractile ring reshapes primordial germ cells to allow bulk cytoplasmic remodeling","authors":"Chelsea Maniscalco, Allison E. Hall, J. Nance","doi":"10.1083/jcb.201906185","DOIUrl":"https://doi.org/10.1083/jcb.201906185","url":null,"abstract":"Maniscalco et al. show that primordial germ cells remodel by assembling a nonmitotic contractile ring. Ring formation requires the RhoGEF ECT-2 and its activator NOP-1 but not centralspindlin, which activates ECT-2 to position the cytokinetic contractile ring during mitosis.","PeriodicalId":343306,"journal":{"name":"The Journal of Cell Biology","volume":"54 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130916715","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: 9
Nanoscopy reveals the layered organization of the sarcomeric H-zone and I-band complexes 纳米显微镜显示了肌共聚物h区和i带配合物的层状组织
The Journal of Cell Biology Pub Date : 2019-12-05 DOI: 10.1083/jcb.201907026
Szilárd Szikora, T. Gajdos, Tibor Novák, Dávid Farkas, István Földi, P. Lénárt, M. Erdélyi, J. Mihály
{"title":"Nanoscopy reveals the layered organization of the sarcomeric H-zone and I-band complexes","authors":"Szilárd Szikora, T. Gajdos, Tibor Novák, Dávid Farkas, István Földi, P. Lénárt, M. Erdélyi, J. Mihály","doi":"10.1083/jcb.201907026","DOIUrl":"https://doi.org/10.1083/jcb.201907026","url":null,"abstract":"Szikora et al. use superresolution microscopy to reveal muscle protein localizations at the nanoscale level. With this protein localization atlas and template-based protein structure modeling, they assemble refined I-band and H-zone models and provide new mechanistic insights into sarcomerogenesis.","PeriodicalId":343306,"journal":{"name":"The Journal of Cell Biology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124645718","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: 25
Gene expression amplification by nuclear speckle association 核斑点关联法扩增基因表达
The Journal of Cell Biology Pub Date : 2019-11-22 DOI: 10.1083/jcb.201904046
Jiah Kim, Neha Chivukula Venkata, Gabriela A Hernandez Gonzalez, Nimish Khanna, A. Belmont
{"title":"Gene expression amplification by nuclear speckle association","authors":"Jiah Kim, Neha Chivukula Venkata, Gabriela A Hernandez Gonzalez, Nimish Khanna, A. Belmont","doi":"10.1083/jcb.201904046","DOIUrl":"https://doi.org/10.1083/jcb.201904046","url":null,"abstract":"Many active genes position near nuclear speckles. Kim et al. show that Hsp70 speckle association correlates with increased nascent transcripts. Live-cell imaging shows that increases in nascent Hsp70 transcripts strictly follow speckle association (∼0–2 min), suggesting that speckle association amplifies gene expression.","PeriodicalId":343306,"journal":{"name":"The Journal of Cell Biology","volume":"28 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132745062","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: 63
CLASP2 binding to curved microtubule tips promotes flux and stabilizes kinetochore attachments CLASP2结合到弯曲的微管尖端促进通量和稳定着丝点附着
The Journal of Cell Biology Pub Date : 2019-11-22 DOI: 10.1083/jcb.201905080
Hugo Girão, Naoyuki Okada, T. Rodrigues, Alexandra Silva, A. C. Figueiredo, Z. García, Tatiana Moutinho‐Santos, I. Hayashi, Jorge E Azevedo, Sandra Macedo-Ribeiro, H. Maiato
{"title":"CLASP2 binding to curved microtubule tips promotes flux and stabilizes kinetochore attachments","authors":"Hugo Girão, Naoyuki Okada, T. Rodrigues, Alexandra Silva, A. C. Figueiredo, Z. García, Tatiana Moutinho‐Santos, I. Hayashi, Jorge E Azevedo, Sandra Macedo-Ribeiro, H. Maiato","doi":"10.1083/jcb.201905080","DOIUrl":"https://doi.org/10.1083/jcb.201905080","url":null,"abstract":"Girão et al. use structure-guided functional mutants of CLASP2 to show that recognition of growing microtubule plus-ends through EB–protein interaction and the ability to associate with curved microtubule protofilaments through TOG2 and TOG3 domains promote growth and stabilization of kinetochore–microtubules required for poleward flux.","PeriodicalId":343306,"journal":{"name":"The Journal of Cell Biology","volume":"23 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125506340","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: 23
Autophagy and cancer: Modulation of cell death pathways and cancer cell adaptations 自噬和癌症:细胞死亡途径和癌细胞适应的调节
The Journal of Cell Biology Pub Date : 2019-11-21 DOI: 10.1083/jcb.201909033
C. Towers, Darya Wodetzki, A. Thorburn
{"title":"Autophagy and cancer: Modulation of cell death pathways and cancer cell adaptations","authors":"C. Towers, Darya Wodetzki, A. Thorburn","doi":"10.1083/jcb.201909033","DOIUrl":"https://doi.org/10.1083/jcb.201909033","url":null,"abstract":"Towers et al. review the complex roles of autophagy in cancer and how autophagy relates to mechanisms of cancer cell death and tumor immunology.","PeriodicalId":343306,"journal":{"name":"The Journal of Cell Biology","volume":"6 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132541471","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: 89
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