Rei Iguchi, Tomoki Kita, Taisei Watanabe, Kyoko Chiba, Shinsuke Niwa
{"title":"Characterizing human KIF1Bβ motor activity by single-molecule motility assays and Caenorhabditis elegans genetics.","authors":"Rei Iguchi, Tomoki Kita, Taisei Watanabe, Kyoko Chiba, Shinsuke Niwa","doi":"10.1242/jcs.261783","DOIUrl":"10.1242/jcs.261783","url":null,"abstract":"<p><p>The axonal transport of synaptic vesicle precursors relies on KIF1A and UNC-104 ortholog motors. In mammals, KIF1Bβ is also responsible for the axonal transport of synaptic vesicle precursors. Mutations in KIF1A and KIF1Bβ lead to a wide range of neuropathies. Although previous studies have revealed the biochemical, biophysical and cell biological properties of KIF1A, and its defects in neurological disorders, the fundamental properties of KIF1Bβ remain elusive. In this study, we determined the motile parameters of KIF1Bβ through single-molecule motility assays. We found that the C-terminal region of KIF1Bβ has an inhibitory role in motor activity. AlphaFold2 prediction suggests that the C-terminal region blocks the motor domain. Additionally, we established simple methods for testing the axonal transport activity of human KIF1Bβ using Caenorhabditis elegans genetics. Taking advantage of these methods, we demonstrated that these assays enable the detection of reduced KIF1Bβ activities, both in vitro and in vivo, caused by a Charcot-Marie-Tooth disease-associated Q98L mutation.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Agustin Rabino, Sahezeel Awadia, Nabaa Ali, Amber Edson, Rafael Garcia-Mata
{"title":"The Scribble-SGEF-Dlg1 complex regulates E-cadherin and ZO-1 stability, turnover and transcription in epithelial cells.","authors":"Agustin Rabino, Sahezeel Awadia, Nabaa Ali, Amber Edson, Rafael Garcia-Mata","doi":"10.1242/jcs.262181","DOIUrl":"10.1242/jcs.262181","url":null,"abstract":"<p><p>SGEF (also known as ARHGEF26), a RhoG specific GEF, can form a ternary complex with the Scribble polarity complex proteins Scribble and Dlg1, which regulates the formation and maintenance of adherens junctions and barrier function of epithelial cells. Notably, silencing SGEF results in a dramatic downregulation of both E-cadherin and ZO-1 (also known as TJP1) protein levels. However, the molecular mechanisms involved in the regulation of this pathway are not known. Here, we describe a novel signaling pathway governed by the Scribble-SGEF-Dlg1 complex. Our results show that the three members of the ternary complex are required to maintain the stability of the apical junctions, ZO-1 protein levels and tight junction (TJ) permeability. In contrast, only SGEF is necessary to regulate E-cadherin levels. The absence of SGEF destabilizes the E-cadherin-catenin complex at the membrane, triggering a positive feedback loop that exacerbates the phenotype through the repression of E-cadherin transcription in a process that involves the internalization of E-cadherin by endocytosis, β-catenin signaling and the transcriptional repressor Slug (also known as SNAI2).</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"HIV-1 assembly - when virology meets biophysics.","authors":"Claire Lacouture, Baptiste Carrio, Cyril Favard, Delphine Muriaux","doi":"10.1242/jcs.262064","DOIUrl":"https://doi.org/10.1242/jcs.262064","url":null,"abstract":"<p><p>Cells naturally produce vesicles that bud from different lipid membranes using dedicated molecular machineries. Enveloped RNA viruses, including human immunodeficiency virus type 1 (HIV-1), also generate particles that bud from host cell membranes by hijacking cellular factors and signaling pathways similar to those involved in the budding of extracellular vesicles. HIV-1 buds from the host cell plasma membrane mainly via the self-assembly of Gag, a structural protein. Gag is a polyprotein that forms assembly complexes containing viral genomic RNA (gRNA), host cell lipids and proteins. HIV-1 Gag binds and segregates host cell plasma membrane lipids while self-assembling simultaneously on the gRNA and the plasma membrane. This self-assembly causes membrane bending and formation of a new viral particle with the help of host cell proteins, likely including cortical actin-associated factors. However, it is unclear whether the energy of Gag self-assembly is sufficient to generate new HIV-1 particles. In this Review, we discuss these processes in the light of the past and recent virology literature, incorporating lessons from studies on the quantitative biophysics of viral self-assembly, and explore how Gag might reorganize the plasma membrane and divert host cell membrane curving proteins and cortical actin-related factors to achieve particle assembly and budding.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"137 19","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Monika Bijata, Alexander Wirth, Jakub Wlodarczyk, Evgeni Ponimaskin
{"title":"The interplay of serotonin 5-HT1A and 5-HT7 receptors in chronic stress.","authors":"Monika Bijata, Alexander Wirth, Jakub Wlodarczyk, Evgeni Ponimaskin","doi":"10.1242/jcs.262219","DOIUrl":"10.1242/jcs.262219","url":null,"abstract":"<p><p>Serotonin regulates multiple physiological and pathological processes in the brain, including mood and cognition. The serotonin receptors 5-HT1AR (also known as HTR1A) and 5-HT7R (also known as HTR7) have emerged as key players in stress-related disorders, particularly depression. These receptors can form heterodimers, which influence their functions. Here, we explored the developmental dynamics of 5-HT1AR and 5-HT7R expression and validated heterodimerization levels in the brain of control and stressed mice. In control animals, we found that there was an increase in 5-HT1AR expression over 5-HT7R in the prefrontal cortex (PFC) and hippocampus during development. Using a chronic unpredictable stress as a depression model, we found an increase in 5-HT7R expression exclusively in the PFC of resilient animals, whereas no changes in 5-HT1AR expression between control and anhedonic mice were obtained. Quantitative in situ analysis of heterodimerization revealed the PFC as the region exhibiting the highest abundance of 5-HT1AR-5-HT7R heterodimers. More importantly, upon chronic stress, the amount of heterodimers was significantly reduced only in PFC of anhedonic mice, whereas it was not affected in resilient animals. These results suggest an important role of brain-region-specific 5-HT1AR-5-HT7R heterodimerization for establishing depressive-like behaviour and for development of resiliency.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The FHA domain is essential for autoinhibition of KIF1A/UNC-104 proteins.","authors":"Shinsuke Niwa, Taisei Watanabe, Kyoko Chiba","doi":"10.1242/jcs.262017","DOIUrl":"10.1242/jcs.262017","url":null,"abstract":"<p><p>KIF1A/UNC-104 proteins, which are members of the kinesin superfamily of motor proteins, play a pivotal role in the axonal transport of synaptic vesicles and their precursors. Drosophila melanogaster UNC-104 (DmUNC-104) is a relatively recently discovered Drosophila kinesin. Although some point mutations that disrupt synapse formation have been identified, the biochemical properties of the DmUNC-104 protein have not been investigated. Here, we prepared recombinant full-length DmUNC-104 protein and determined its biochemical features. We analyzed the effect of a previously identified missense mutation in the forkhead-associated (FHA) domain, called bristly (bris). The bris mutation strongly promoted the dimerization of DmUNC-104 protein, whereas wild-type DmUNC-104 was a mixture of monomers and dimers. We further tested the G618R mutation near the FHA domain, which was previously shown to disrupt the autoinhibition of Caenorhabditis elegans UNC-104. The biochemical properties of the G618R mutant recapitulated those of the bris mutant. Finally, we found that disease-associated mutations also promote the dimerization of DmUNC-104. Collectively, our results suggest that the FHA domain is essential for autoinhibition of KIF1A/UNC-104 proteins, and that abnormal dimerization of KIF1A might be linked to human diseases.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Luisa F Arias Padilla, Jonathan Munera Lopez, Aika Shibata, John M Murray, Ke Hu
{"title":"The initiation and early development of apical-basal polarity in Toxoplasma gondii.","authors":"Luisa F Arias Padilla, Jonathan Munera Lopez, Aika Shibata, John M Murray, Ke Hu","doi":"10.1242/jcs.263436","DOIUrl":"10.1242/jcs.263436","url":null,"abstract":"<p><p>The body plan of the human parasite Toxoplasma gondii has a well-defined polarity. The minus ends of the 22 cortical microtubules are anchored to the apical polar ring, which is a putative microtubule-organizing center. The basal complex caps and constricts the parasite posterior end and is crucial for cytokinesis. How this apical-basal polarity is initiated is unknown. Here, we have examined the development of the apical polar ring and the basal complex using expansion microscopy. We found that substructures in the apical polar ring have different sensitivities to perturbations. In addition, apical-basal differentiation is already established upon nucleation of the cortical microtubule array: arc forms of the apical polar ring and basal complex associate with opposite ends of the microtubules. As the nascent daughter framework grows towards the centrioles, the apical and basal arcs co-develop ahead of the microtubule array. Finally, two apical polar ring components, APR2 and KinesinA, act synergistically. The removal of individual proteins has a modest impact on the lytic cycle. However, the loss of both proteins results in abnormalities in the microtubule array and in highly reduced plaquing and invasion efficiency.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaohuan Sun, Wenqian Yu, Peter W Baas, Kazuhito Toyooka, Liang Qiang
{"title":"Antagonistic roles of tau and MAP6 in regulating neuronal development.","authors":"Xiaohuan Sun, Wenqian Yu, Peter W Baas, Kazuhito Toyooka, Liang Qiang","doi":"10.1242/jcs.261966","DOIUrl":"10.1242/jcs.261966","url":null,"abstract":"<p><p>Association of tau (encoded by Mapt) with microtubules causes them to be labile, whereas association of MAP6 with microtubules causes them to be stable. As axons differentiate and grow, tau and MAP6 segregate from one another on individual microtubules, resulting in the formation of stable and labile domains. The functional significance of the yin-yang relationship between tau and MAP6 remains speculative, with one idea being that such a relationship assists in balancing morphological stability with plasticity. Here, using primary rodent neuronal cultures, we show that tau depletion has opposite effects compared to MAP6 depletion on the rate of neuronal development, the efficiency of growth cone turning, and the number of neuronal processes and axonal branches. Opposite effects to those seen with tau depletion were also observed on the rate of neuronal migration, in an in vivo assay, when MAP6 was depleted. When tau and MAP6 were depleted together from neuronal cultures, the morphological phenotypes negated one another. Although tau and MAP6 are multifunctional proteins, our results suggest that the observed effects on neuronal development are likely due to their opposite roles in regulating microtubule stability.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cecilia Alejandra Vazquez,Beatriz Escudero-Pérez,Jennifer M Hayashi,Kristoffer E Leon,João Paulo Moreira,Mayra Alejandra Castañeda Cataña,Allison Groseth,Melanie Ott,Lisa Oestereich,César Muñoz-Fontela,Cybele Carina Garcia,Sandra Myriam Cordo
{"title":"Intracellular lipid droplets are exploited by Junín virus: a nucleoprotein-dependent process.","authors":"Cecilia Alejandra Vazquez,Beatriz Escudero-Pérez,Jennifer M Hayashi,Kristoffer E Leon,João Paulo Moreira,Mayra Alejandra Castañeda Cataña,Allison Groseth,Melanie Ott,Lisa Oestereich,César Muñoz-Fontela,Cybele Carina Garcia,Sandra Myriam Cordo","doi":"10.1242/jcs.261745","DOIUrl":"https://doi.org/10.1242/jcs.261745","url":null,"abstract":"Lipid droplets (LDs) are organelles involved in lipid storage, maintenance of energy homeostasis, protein sequestration, signaling events and inter-organelle interactions. Recently, LDs have been shown to favor the replication of members from different viral families, such as the Flaviviridae and Coronaviridae. In this work, we found that LDs are essential organelles for members of the Arenaviridae family. A virus-driven reduction of LDs number was observed in cultures infected with Junín mammarenavirus (JUNV), caused in part by action of the viral nucleoprotein. To note, we identified a new pool of nucleoprotein and viral RNA that localize in the vicinity of LDs, suggesting that LDs play a role during the viral replication cycle. Regarding the mechanism behind LDs exhaustion, we found evidence that lipophagy is involved in LD degradation with the resulting fatty acids being substrates of fatty acid β-oxidation which fuels viral multiplication. This work highlights the importance of LDs during the replication cycle of JUNV, contributing to the knowledge of the metabolic changes these mammarenaviruses cause in their hosts.","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"97 1 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Principles and regulation of mechanosensing.","authors":"Stefano Sala, Alexia Caillier, Patrick W Oakes","doi":"10.1242/jcs.261338","DOIUrl":"10.1242/jcs.261338","url":null,"abstract":"<p><p>Research over the past two decades has highlighted that mechanical signaling is a crucial component in regulating biological processes. Although many processes and proteins are termed 'mechanosensitive', the underlying mechanisms involved in mechanosensing can vary greatly. Recent studies have also identified mechanosensing behaviors that can be regulated independently of applied force. This important finding has major implications for our understanding of downstream mechanotransduction, the process by which mechanical signals are converted into biochemical signals, as it offers another layer of biochemical regulatory control for these crucial signaling pathways. In this Review, we discuss the different molecular and cellular mechanisms of mechanosensing, how these processes are regulated and their effects on downstream mechanotransduction. Together, these discussions provide an important perspective on how cells and tissues control the ways in which they sense and interpret mechanical signals.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"137 18","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11423818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Evgeniya M Pukhovaya, João Jacob Ramalho, Dolf Weijers
{"title":"Polar targeting of proteins - a green perspective.","authors":"Evgeniya M Pukhovaya, João Jacob Ramalho, Dolf Weijers","doi":"10.1242/jcs.262068","DOIUrl":"https://doi.org/10.1242/jcs.262068","url":null,"abstract":"<p><p>Cell polarity - the asymmetric distribution of molecules and cell structures within the cell - is a feature that almost all cells possess. Even though the cytoskeleton and other intracellular organelles can have a direction and guide protein distribution, the plasma membrane is, in many cases, essential for the asymmetric localization of proteins because it helps to concentrate proteins and restrict their localization. Indeed, many proteins that exhibit asymmetric or polarized localization are either embedded in the PM or located close to it in the cellular cortex. Such proteins, which we refer to here as 'polar proteins', use various mechanisms of membrane targeting, including vesicle trafficking, direct phospholipid binding, or membrane anchoring mediated by post-translational modifications or binding to other proteins. These mechanisms are often shared with non-polar proteins, yet the unique combinations of several mechanisms or protein-specific factors assure the asymmetric distribution of polar proteins. Although there is a relatively detailed understanding of polar protein membrane targeting mechanisms in animal and yeast models, knowledge in plants is more fragmented and focused on a limited number of known polar proteins in different contexts. In this Review, we combine the current knowledge of membrane targeting mechanisms and factors for known plant transmembrane and cortical proteins and compare these with the mechanisms elucidated in non-plant systems. We classify the known factors as general or polarity specific, and we highlight areas where more knowledge is needed to construct an understanding of general polar targeting mechanisms in plants or to resolve controversies.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"137 18","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}