Journal of Cell Biology最新文献

Divergent Rickettsia species exhibit distinct mechanisms of actin-based motility. 不同的立克次体物种表现出不同的基于肌动蛋白的运动机制。

IF 6.4 1区生物学

Journal of Cell Biology Pub Date : 2026-07-06 Epub Date: 2026-04-28 DOI: 10.1083/jcb.202508117

Meghan C Bacher, Julie E Choe, Jiawen Jiang, Joanna M Idrovo, Joshua T Del Mundo, Michal Hammel, Matthew D Welch

{"title":"Divergent Rickettsia species exhibit distinct mechanisms of actin-based motility.","authors":"Meghan C Bacher, Julie E Choe, Jiawen Jiang, Joanna M Idrovo, Joshua T Del Mundo, Michal Hammel, Matthew D Welch","doi":"10.1083/jcb.202508117","DOIUrl":"10.1083/jcb.202508117","url":null,"abstract":"Many Rickettsia species undergo actin-based motility to promote cell-cell spread during infection. Rickettsial genomes often encode two motility effectors, RickA and Sca2, which in the spotted fever group I species, Rickettsia parkeri act by activating the host Arp2/3 complex and by mimicking eukaryotic formins, respectively. The function of RickA and Sca2 orthologs in the distantly related species Rickettsia bellii was unclear. We report that R. bellii RickA activates the host Arp2/3 complex but has no discernible role in bacterial motility. The R. bellii Sca2 ortholog, Sca2/6, nucleates and elongates actin with a flexible structure and an unusual actin monomer-binding motif in a mechanism distinct from formins or other microbial actin nucleators. R. bellii motility is solely correlated with Sca2/6 localization and, compared with R. parkeri motility, is slow and meandering, generating distinctly organized actin tails. The evolutionary flexibility in the mechanism and regulation of rickettsial actin-based motility suggests similar adaptability for other microbes.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 7","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13137875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772748","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

NASP functions in the cytoplasm to prevent histone H3 aggregation during early embryogenesis. 在胚胎发生早期，NASP在细胞质中起阻止组蛋白H3聚集的作用。

IF 6.4 1区生物学

Journal of Cell Biology Pub Date : 2026-07-06 Epub Date: 2026-05-06 DOI: 10.1083/jcb.202511182

Mohit Das, Eli Coronado-Chavez, Anusha D Bhatt, Reyhaneh Tirgar, Amanda A Amodeo, Jared T Nordman

引用次数: 0

Regulation of the Cell Wall Integrity pathway at the contact site between mating partners in yeast. 酵母交配伴侣接触部位细胞壁完整性通路的调控。

IF 6.4 1区生物学

Journal of Cell Biology Pub Date : 2026-07-06 Epub Date: 2026-04-30 DOI: 10.1083/jcb.202508068

Erin R Curtis, Aarshi Jain, Daniel J Lew

引用次数: 0

Optogenetic control of PLC-γ1 activity directs cell motility. PLC-γ - 1活性的光遗传学控制指导细胞运动。

IF 6.4 1区生物学

Journal of Cell Biology Pub Date : 2026-07-06 Epub Date: 2026-05-05 DOI: 10.1083/jcb.202507177

Ravikanth Appalabhotla, Priscila F Siesser, Harrison Truscott, Nicole Hajicek, John Sondek, James E Bear, Jason M Haugh

{"title":"Optogenetic control of PLC-γ1 activity directs cell motility.","authors":"Ravikanth Appalabhotla, Priscila F Siesser, Harrison Truscott, Nicole Hajicek, John Sondek, James E Bear, Jason M Haugh","doi":"10.1083/jcb.202507177","DOIUrl":"https://doi.org/10.1083/jcb.202507177","url":null,"abstract":"Phospholipase C-γ1 (PLC-γ1) signaling is required for mesenchymal chemotaxis, but is it sufficient to bias motility? PLC-γ1 enzyme activity is basally autoinhibited, and light-controlled membrane recruitment of wild-type PLC-γ1 (OptoPLC-γ1) in Plcg1-null fibroblasts does not trigger lipid hydrolysis, complicating efforts to isolate its contribution. Utilizing cancer-associated mutations to investigate the regulatory logic of PLC-γ1, we demonstrate that a hallmark of enzyme activity, phosphorylated Tyr783, is not a proxy for activity level, but is rather a marker of dysregulated autoinhibition. Accordingly, OptoPLC-γ1 with a deregulating mutation (P867R, S345F, or D1165H) exhibits elevated phosphorylation, and membrane localization of such is sufficient to activate substrate hydrolysis and concomitant motility responses. In particular, local recruitment of OptoPLC-γ1 S345F polarizes cell motility and migration on demand. This response is spatially dose-sensitive and only partially reduced by blocking canonical PLC-γ1 signaling, yet is lipase-dependent. Our findings reframe the interpretation of PLC-γ1 regulation and demonstrate that local activation of PLC-γ1 is sufficient to direct cell motility.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 7","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838400","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

Bitesize bundles F-actin and influences actin remodeling in syncytial Drosophila embryo development. 咬大小捆绑f -肌动蛋白并影响肌动蛋白在合胞果蝇胚胎发育中的重塑。

IF 6.4 1区生物学

Journal of Cell Biology Pub Date : 2026-07-06 Epub Date: 2026-05-06 DOI: 10.1083/jcb.202306071

Anna R Yeh, Gregory J Hoeprich, Anthony D McDougal, Bruce L Goode, Adam C Martin

{"title":"Bitesize bundles F-actin and influences actin remodeling in syncytial Drosophila embryo development.","authors":"Anna R Yeh, Gregory J Hoeprich, Anthony D McDougal, Bruce L Goode, Adam C Martin","doi":"10.1083/jcb.202306071","DOIUrl":"https://doi.org/10.1083/jcb.202306071","url":null,"abstract":"Actin networks undergo rearrangements that influence cell shape. Actin network organization is regulated by a host of actin-binding proteins. The Drosophila synaptotagmin-like protein, bitesize (Btsz), organizes actin at epithelial cell apical junctions in a manner that depends on its interaction with the actin-binding protein, moesin. Using RNAi, we showed that Btsz functions at earlier, syncytial stages of Drosophila embryo development. Btsz is required to stabilize pseudo-cleavage furrows, preventing metaphase spindle collisions and nuclear fallout prior to cellularization. While previous studies have focused on Btsz function through moesin, we find that phosphorylated moesin localized to the nuclear envelope and was not enriched at pseudo-cleavage furrows, suggesting a moesin-independent function for Btsz in syncytial embryos. Consistent with this, mutants that affected all moesin-binding domain isoforms did not recapitulate pan-isoform Btsz depletion and we find that the C-terminal half of Btsz cooperatively binds to and bundles F-actin. We propose that synaptotagmin-like proteins directly regulate actin organization during syncytial Drosophila development.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 7","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838351","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

Mitochondrially tethered Mmm1 can function as a sole lipid transporter at ER-mitochondria contacts. 线粒体拴系的mm1可以在er -线粒体接触处作为唯一的脂质转运蛋白。

IF 6.4 1区生物学

Journal of Cell Biology Pub Date : 2026-07-06 Epub Date: 2026-05-07 DOI: 10.1083/jcb.202411196

Christian Covill-Cooke, Takashi Hirashima, Shin Kawano, Joe Ganellin, Andrew Moody, Sabine N S van Schie, Arun T John Peter, Chika Horie Saito, Toshiya Endo, Benoît Kornmann

{"title":"Mitochondrially tethered Mmm1 can function as a sole lipid transporter at ER-mitochondria contacts.","authors":"Christian Covill-Cooke, Takashi Hirashima, Shin Kawano, Joe Ganellin, Andrew Moody, Sabine N S van Schie, Arun T John Peter, Chika Horie Saito, Toshiya Endo, Benoît Kornmann","doi":"10.1083/jcb.202411196","DOIUrl":"10.1083/jcb.202411196","url":null,"abstract":"Yeast mitochondria receive the majority of their lipids from the ER via the heterotetrameric ERMES lipid transport complex. This complex is thought to establish a lipid-transporting bridge of fixed composition spanning the space between both organelles. Intriguingly, however, some of the lipid-transporting components of the complex can be replaced by an artificial ER-mitochondria tether without lipid transport activity, questioning ERMES' relevance in lipid transport. Here, we show that Mmm1, one of the four ERMES subunits, alone is sufficient to support ERMES function when it is artificially tethered to mitochondria, provided its lipid-binding domain is intact. Combined with our previous finding that the absence of Mdm12 and Mdm34 can be rescued by the presence of Mmm1 and the artificial tethering protein ChiMERA, our results suggest that Mmm1 can act as the sole lipid transporter at the ER-mitochondrial contact sites, provided that Mdm10 is present, even in the absence of the other two subunits. Thus, our work reconciles ERMES' importance in lipid transport with the fact that the lipid transport activity of some of its components is not strictly necessary for function.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 7","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838370","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

Time-resolved tmFRET reveals GTP-coupled conformational changes in Mfn1. 时间分辨tmFRET揭示了gtp耦合的Mfn1构象变化。

IF 6.4 1区生物学

Journal of Cell Biology Pub Date : 2026-07-06 Epub Date: 2026-05-04 DOI: 10.1083/jcb.202511077

Sophie M Hurwitz, William N Zagotta, Sharona E Gordon, Suzanne Hoppins

{"title":"Time-resolved tmFRET reveals GTP-coupled conformational changes in Mfn1.","authors":"Sophie M Hurwitz, William N Zagotta, Sharona E Gordon, Suzanne Hoppins","doi":"10.1083/jcb.202511077","DOIUrl":"https://doi.org/10.1083/jcb.202511077","url":null,"abstract":"Outer mitochondrial membrane fusion is mediated by the mitofusin paralogs Mfn1 and Mfn2. Nucleotide-driven self-assembly and conformational changes are required for regulated membrane fusion activity, but the allosteric mechanisms remain enigmatic due to incomplete structural information. In this study, we investigate the GTP-coupled conformational dynamics of Mfn1 using time-resolved transition metal ion fluorescence resonance energy transfer (tmFRET). Using the minimal Mfn1 construct with the GTPase domain and helical bundle 1 (HB1) connected by Hinge 2, we engineered FRET pairs by incorporating a fluorescent noncanonical amino acid donor and a metal ion acceptor. For each state of the catalytic cycle, we measured tmFRET with fluorescence lifetimes and determined distance distributions, which can capture complex structural heterogeneity. Our distance measurements for the GDP-bound state matched predictions from the atomic resolution structure, establishing that the same open state, with GTPase and HB1 domains far apart, exists in solution. Our data reveal that the transition state is not a single closed state with HB1 stably contacting the GTPase domain. Rather, the distance distributions indicate that the presence of GDP + Pi results in an equilibrium between the open and closed states. We also captured the GTP-bound and nucleotide-free states of Mfn1. GTP binding favors the open state, and the conformation of the apo state is distinct from any nucleotide-bound state. Together, these findings redefine our understanding of GTP-driven conformational dynamics in Mfn1, demonstrating an unexpected conformational reversal in a single catalytic cycle and a heterogeneous transition state ensemble with implications for the mechanism and regulation of mitochondrial membrane fusion.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 7","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147814848","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

Ultrastructure of dopaminergic varicosities revealed by cryo-correlative light and electron microscopy. 低温相关光镜和电镜观察多巴胺能变异的超微结构。

IF 6.4 1区生物学

Journal of Cell Biology Pub Date : 2026-06-01 Epub Date: 2026-05-04 DOI: 10.1083/jcb.202503059

Matthew Domenic Lycas, Dustin R Morado, Ulrik Gether, John A G Briggs, Simon Erlendsson

{"title":"Ultrastructure of dopaminergic varicosities revealed by cryo-correlative light and electron microscopy.","authors":"Matthew Domenic Lycas, Dustin R Morado, Ulrik Gether, John A G Briggs, Simon Erlendsson","doi":"10.1083/jcb.202503059","DOIUrl":"https://doi.org/10.1083/jcb.202503059","url":null,"abstract":"Dopaminergic neurons are fundamental in governing motivation, movement, and many aspects of cognition. The targeted modulation of dopaminergic signaling serves as a cornerstone in developing therapeutic interventions for conditions such as Parkinson's disease, schizophrenia, and addiction. Despite the pivotal role of dopaminergic neurons, the ultrastructure of dopaminergic synapses remains poorly understood. Here, we establish and utilize a cryo-correlative light and electron microscopy process to investigate the micro/nanoscale architecture and organelle content of dopaminergic varicosities. Using cryo-electron tomography and subtomogram averaging, we demonstrate the ability to resolve in situ complex structures of the TRiC/CCT chaperone and the vacuolar-type ATPase. We combine our experimental setup with pharmacological treatments using dopamine or haloperidol, showing bidirectional modulation of vesicular content and mitochondrial calcium phosphate deposition. These findings contribute to our understanding of the composition and (re)organization of dopaminergic varicosities and provide a methodological platform for further studies of the structure and cell biology of dopaminergic neurons and their responses.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 6","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147814764","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

LGL-1 and the RhoGAP protein PAC-1 redundantly polarize the Caenorhabditis elegans embryonic epidermis. LGL-1和RhoGAP蛋白PAC-1冗余极化秀丽隐杆线虫胚胎表皮。

IF 6.4 1区生物学

Journal of Cell Biology Pub Date : 2026-06-01 Epub Date: 2026-05-05 DOI: 10.1083/jcb.202601031

Olga D Jarosińska, Amalia Riga, Hala Zahreddine Fahs, Joren M Woeltjes, Ruben Schmidt, Fathima S Refai, Suma Gopinadhan, Kristin C Gunsalus, Mike Boxem

{"title":"LGL-1 and the RhoGAP protein PAC-1 redundantly polarize the Caenorhabditis elegans embryonic epidermis.","authors":"Olga D Jarosińska, Amalia Riga, Hala Zahreddine Fahs, Joren M Woeltjes, Ruben Schmidt, Fathima S Refai, Suma Gopinadhan, Kristin C Gunsalus, Mike Boxem","doi":"10.1083/jcb.202601031","DOIUrl":"https://doi.org/10.1083/jcb.202601031","url":null,"abstract":"Apical-basal polarity is essential for epithelial organization and function and is established by conserved cortical polarity proteins. However, the requirements for canonical polarity factors vary between tissues and organisms. For example, the basolateral protein lethal giant larvae is essential for epithelial polarity in Drosophila but dispensable in Caenorhabditis elegans. To better define the epithelial polarity program in C. elegans, we performed a genome-wide RNAi screen for synthetic lethality with lgl-1. Combined loss of LGL-1 and the RhoGAP PAC-1 caused embryonic lethality due to elongation defects and epidermal rupture. Epidermal cells showed expansion of the apical domain and aPKC, accompanied by mislocalization of junctional proteins and LET-413Scribble. These defects indicate overactivity of apical polarity determinants. Consistently, partial inactivation of aPKC or CDC-42 suppressed lethality in pac-1; lgl-1 animals. Together, our results identify PAC-1 and LGL-1 as redundant inhibitors of apical polarity in the C. elegans embryonic epidermis and provide new insights into how conserved mechanisms are adapted across species.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 6","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838267","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

Spatial inhibition of RhoA by RhoGAP15B promotes protrusive activity during collective migration. RhoGAP15B对RhoA的空间抑制促进了集体迁移过程中的突出活动。

IF 6.4 1区生物学

Journal of Cell Biology Pub Date : 2026-06-01 Epub Date: 2026-04-09 DOI: 10.1083/jcb.202511004

Vítor Yang, Cristian Marchant, Bing Liu, Mariana Osswald, Jesus Lopez-Gay, Yohanns Bellaïche, Xiaobo Wang, Eurico Morais-de-Sá

{"title":"Spatial inhibition of RhoA by RhoGAP15B promotes protrusive activity during collective migration.","authors":"Vítor Yang, Cristian Marchant, Bing Liu, Mariana Osswald, Jesus Lopez-Gay, Yohanns Bellaïche, Xiaobo Wang, Eurico Morais-de-Sá","doi":"10.1083/jcb.202511004","DOIUrl":"10.1083/jcb.202511004","url":null,"abstract":"The Rho family GTPases RhoA, Rac1, and Cdc42 are well-established regulators of collective migration by driving the formation of cellular protrusions and by regulating actomyosin contraction and adhesion. However, how their activation and inhibition are spatially and temporally coordinated remains unclear. Using GFP knock-in lines, we systematically characterized the localization patterns of all Drosophila RhoGEFs (activators) and RhoGAPs (inhibitors) in border cells, an in vivo model of collective migration. We have further combined RNAi screening with GFP-based validation of depletion efficiency to assess the functional significance of those RhoGEFs/GAPs expressed in border cells. This identified RhoGAP15B as a localized inhibitor of RhoA activity at the border cell cortex. RhoGAP15B regulates cluster morphology and is enriched at the leading cell front, where it restrains actomyosin contractility to promote protrusive behavior. Our findings reveal RhoGAP15B as a key spatial RhoA regulator and highlight that patterned RhoGAP and RhoGEF activities are essential for coordinating cortical contraction and protrusion dynamics during collective migration.","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 6","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639030","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