Pub Date : 2020-07-07DOI: 10.1101/2020.07.07.192609
Yijun Zhang, J. Seemann
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.
{"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}
Pub Date : 2020-07-02DOI: 10.1101/2020.07.01.182980
Nan Xin, Jenni Durieux, Chun-hu Yang, Suzanne C. Wolff, Hyun-Eui Kim, A. Dillin
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.
{"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}
J. Armistead, J. Hatzold, Anna van Roye, Evelin Fahle, M. Hammerschmidt
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.
{"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}
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
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.
{"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}
P. Atherton, Franziska Lausecker, Alexandre F. Carisey, A. Gilmore, D. Critchley, I. Barsukov, C. Ballestrem
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.
{"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}
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.
{"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}
Szilárd Szikora, T. Gajdos, Tibor Novák, Dávid Farkas, István Földi, P. Lénárt, M. Erdélyi, J. Mihály
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.
{"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}
Jiah Kim, Neha Chivukula Venkata, Gabriela A Hernandez Gonzalez, Nimish Khanna, A. Belmont
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.
{"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}
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
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.
{"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}
Towers et al. review the complex roles of autophagy in cancer and how autophagy relates to mechanisms of cancer cell death and tumor immunology.
Towers等人回顾了自噬在癌症中的复杂作用，以及自噬与癌细胞死亡和肿瘤免疫学机制的关系。
{"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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：