Biology of the Cell最新文献

{"title":"The microtubule lattice: a brief historical perspective","authors":"Denis Chrétien,&nbsp;Charlotte Guyomar","doi":"10.1111/boc.202300004","DOIUrl":"10.1111/boc.202300004","url":null,"abstract":"<p>At first glance, the structure of a microtubule is simple. Globular α- and β-tubulin subunits form constitutive heterodimers that align head-to-tail in protofilaments. In the most common configuration, 13 protofilaments associate laterally with a slight longitudinal stagger that results in a left-handed 3-start helix featuring lateral associations between tubulin subunits. This seemingly straightforward description is actually based on almost half a century of research aimed at understanding how tubulin dimers interact within the microtubule lattice. But while we start to have a good overview of their architecture in vitro, our knowledge of microtubule-lattice organization in vivo is nowhere near to being complete.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"115 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.202300004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9476582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A journey in UPR modelling","authors":"Ilaria Pontisso,&nbsp;Roberto Ornelas-Guevara,&nbsp;Laurent Combettes,&nbsp;Geneviève Dupont","doi":"10.1111/boc.202200111","DOIUrl":"10.1111/boc.202200111","url":null,"abstract":"<p>Protein folding and protein maturation largely occur in the controlled environment of the Endoplasmic Reticulum (ER). Perturbation to the correct functioning of this organelle leads to altered proteostasis and accumulation of misfolded proteins in the ER lumen. This condition is commonly known as ER stress and is appearing as an important contributor in the pathogenesis of several human diseases. Monitoring of the quality control processes is mediated by the Unfolded Protein Response (UPR). This response consists in a complex network of signalling pathways that aim to restore protein folding and ER homeostasis. Conditions in which UPR is not able to overcome ER stress lead to a switch of the UPR signalling program from an adaptive to a pro-apoptotic one, revealing a key role of UPR in modulating cell fate decisions. Because of its high complexity and its involvement in the regulation of different cellular outcomes, UPR has been the centre of the development of computational models, which tried to better dissect the role of UPR or of its specific components in several contexts. In this review, we go through the existing mathematical models of UPR. We emphasize how their study contributed to an improved characterization of the role of this intricate response in the modulation of cellular functions.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"115 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9262472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Get in and get out: Remodeling of the cellular actin cytoskeleton upon HIV-1 infection","authors":"Thomas Serrano,&nbsp;Stéphane Frémont,&nbsp;Arnaud Echard","doi":"10.1111/boc.202200085","DOIUrl":"10.1111/boc.202200085","url":null,"abstract":"<p>The human immunodeficiency virus type 1 (HIV-1) is an intracellular pathogen whose replication cycle strictly depends on the host cell molecular machinery. HIV-1 crosses twice the plasma membrane, to get in and to get out of the cell. Therefore, the first and the last line of intracellular component encountered by the virus is the cortical actin network. Here, we review the role of actin and actin-related proteins in HIV-1 entry, assembly, budding, and release. We first highlight the mechanisms controlling actin polymerization at the entry site that promote the clustering of HIV-1 receptors, a crucial step for the virus to fuse with the plasma membrane. Then, we describe how actin is transiently depolymerized locally to allow the capsid to cross the actin cortex, before migrating towards the nucleus. Finally, we review the role of several actin-binding proteins in actin remodeling events required for membrane deformation and curvature at the viral assembly site as well as for virus release. Strikingly, it appears that common actin-regulating pathways are involved in viral entry and exit. However, while the role of actin remodeling during entry is well understood, this is not the case during exit. We discuss remaining challenges regarding the actin-dependent mechanisms involved in HIV-1 entry and exit, and how they could be overcome.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"115 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9255591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissection of the autophagic route in oocytes from atretic follicles","authors":"Abraham Castro-Cruz,&nbsp;Olga M. Echeverría,&nbsp;Luis Sánchez-Sánchez,&nbsp;Israel Muñoz-Velasco,&nbsp;Silvia Juárez-Chavero,&nbsp;Nayeli Torres-Ramírez,&nbsp;Gerardo H. Vázquez-Nin,&nbsp;María Luisa Escobar","doi":"10.1111/boc.202200046","DOIUrl":"10.1111/boc.202200046","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background Information</h3>\u0000 \u0000 <p>Autophagy is a conserved process that functions as a cytoprotective mechanism; it may function as a cell death process called programmed cell death type II. There is considerable evidence for the presence of autophagic cell death during oocyte elimination in prepubertal rats. However, the mechanisms involved in this process have not been deciphered.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our observations revealed autophagic cell death in oocytes with increased labeling of the autophagic proteins Beclin 1, light chain 3 A (LC3 A), and lysosomal-associated membrane protein 1 (Lamp1). Furthermore, mTOR and phosphorylated (p)-mTOR (S2448) proteins were significantly decreased in oocytes with increased levels of autophagic proteins, indicating autophagic activation. Moreover, phosphorylated protein kinase B (p-AKT) was not expressed by oocytes, but mitogen-activated protein kinase/extracellular signalregulated kinase (MAPK/ERK) signaling was observed. Additionally, selective and elevated mitochondrial degradation was identified in altered oocytes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>All these results suggest that mTOR downregulation, which promotes autophagy, could be mediated by low energy levels and sustained starvation involving the phosphoinositide 3-kinase (PI3K)/AKT/mTOR and MAPK/ERK pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>In this work, we analyzed the manner in which autophagy is carried out in oocytes undergoing autophagic cell death by studying the behavior of proteins involved in different steps of the autophagic pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"115 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2022-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.202200046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9096293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prohibitin1 maintains mitochondrial quality in isoproterenol-induced cardiac hypertrophy in H9C2 cells","authors":"Moumita Chakrabarti,&nbsp;Ganesh Kumar Raut,&nbsp;Nishant Jain,&nbsp;Manika Pal Bhadra","doi":"10.1111/boc.202200094","DOIUrl":"10.1111/boc.202200094","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background Information</h3>\u0000 \u0000 <p>Various types of stress initially induce a state of cardiac hypertrophy (CH) in the heart. But, persistent escalation of cardiac stress leads to progression from an adaptive physiological to a maladaptive pathological state. So, elucidating molecular mechanisms that can attenuate CH is imperative in developing cardiac therapies. Previously, we showed that Prohibitin1 (PHB1) has a protective role in CH-induced oxidative stress. Nevertheless, it is unclear how PHB1, a mitochondrial protein, has a protective role in CH. Therefore, we hypothesized that PHB1 maintains mitochondrial quality in CH. To test this hypothesis, we used Isoproterenol (ISO) to induce CH in H9C2 cells overexpressing PHB1 and elucidated mitochondrial quality control pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that overexpressing PHB1 attenuates ISO-induced CH and restores mitochondrial morphology in H9C2 cells. In addition, PHB1 blocks the pro-hypertrophic IGF1R/AKT pathway and restores the mitochondrial membrane polarization in ISO-treated cells. We observed that overexpressing PHB1 promotes mitochondrial biogenesis, improves mitochondrial respiratory capacity, and triggers mitophagy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We conclude that PHB1 maintains mitochondrial quality in ISO-induced CH in H9C2 cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>Based on our results, we suggest that small molecules that induce PHB1 in cardiac cells may prove beneficial in developing cardiac therapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"115 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10701342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time-resolved single virus tracking and spectral imaging to understand HIV-1 entry and fusion","authors":"Sergi Padilla-Parra","doi":"10.1111/boc.202200082","DOIUrl":"10.1111/boc.202200082","url":null,"abstract":"<p>Single Virus Tracking (SVT) is a key technique to understand how individual viral particles evolve during the infection cycle. In the case of the human immunodeficiency virus (HIV-1), this technology, which can be employed using a simple and affordable wide-field microscope, has proven to be very useful in the first steps of infection, such as the kinetics of the fusion reaction or the point of fusion within live cells. Here, we describe how SVT in combination with other spectral imaging approaches is a powerful technique to illuminate crucial mechanistic aspects of the HIV-1 fusion reaction. We also stress the role of our laboratory in elucidating a few mechanistic aspects of retroviral fusion employing SVT such as: (i) the role of dynamin, (ii) how metabolism modulates membrane composition and cholesterol and its impact in fusion, (iii) the importance of envelope glycoprotein (Env) intra- and inter-molecular dynamics for neutralization, or (iv) the time-resolved fusion stoichiometry in three characteristic steps for the HIV-1 prefusion step. These observations constitute a good testimony of the complexity of retroviral fusion and show the strength of SVT when applied to live cells and combined with quantitative spectral approaches. Finally, we propose several crucial remaining questions around HIV-1 fusion and how the combined use of these technologies, always in live cells, will be able to shed light into the intricacies of arguably the most important step of the HIV-1 infection cycle.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"115 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2022-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.202200082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9390671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A snapshot of protein trafficking in SARS-CoV-2 infection","authors":"Vibhu Prasad,&nbsp;Ralf Bartenschlager","doi":"10.1111/boc.202200073","DOIUrl":"10.1111/boc.202200073","url":null,"abstract":"<p>SARS-CoV-2 is a human pathogenic virus responsible for the COVID-19 (coronavirus disease 2019) pandemic. The infection cycle of SARS-CoV-2 involves several related steps, including virus entry, gene expression, RNA replication, assembly of infectious virions and their egress. For all of these steps, the virus relies on and exploits host cell factors, cellular organelles, and processes such as endocytosis, nuclear transport, protein secretion, metabolite transport at membrane contact sites (MSC) and exocytotic pathways. To do this, SARS-CoV-2 has evolved multifunctional viral proteins that hijack cellular factors and modulate their function by unique strategies. In this Review, we highlight cellular trafficking factors, processes, and organelles of relevance to the SARS-CoV-2 infection cycle and how viral proteins make use of and perturb cellular transport during the viral infection cycle.</p>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"115 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2022-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9874443/pdf/BOC-9999-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9225112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ribonucleoprotein transport in Negative Strand RNA viruses","authors":"Cédric Diot,&nbsp;Gina Cosentino,&nbsp;Marie-Anne Rameix-Welti","doi":"10.1111/boc.202200059","DOIUrl":"10.1111/boc.202200059","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Negative-sense, single-stranded RNA (-ssRNA) viruses comprise some of the deadliest human pathogens (Ebola, rabies, influenza A viruses etc.). Developing therapeutic tools relies on a better understanding of their multiplication cycle. For these viruses, the genome replication and transcription activities most-often segregate in membrane-less environments called inclusion bodies (IBs) or viral factories. These “organelles” usually locate far from the cell surface from where new virions are released, and -ssRNA viruses do not encode for transport factors. The efficient trafficking of the genome progeny toward the cell surface is most often ensured by mechanisms co-opting the cellular machineries.</p>\u0000 \u0000 <p>In this review, for each -ssRNA viral family, we cover the methods employed to characterize these host-virus interactions, the strategies used by the viruses to promote the virus genome transport, and the current gaps in the literature. Finally, we highlight how Rab11 has emerged as a target of choice for the intracellular transport of -ssRNA virus genomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"115 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2022-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.202200059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10836975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 inhibition of MDM2 slows cell proliferation and activates apoptosis in ADPKD cell lines","authors":"Simone Patergnani,&nbsp;Antonino Giattino,&nbsp;Nicoletta Bianchi,&nbsp;Carlotta Giorgi,&nbsp;Paolo Pinton,&nbsp;Gianluca Aguiari","doi":"10.1111/boc.202200037","DOIUrl":"10.1111/boc.202200037","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Autosomal dominant polycystic kidney disease (ADPKD) is characterised by progressive cysts formation and renal enlargement that in most of cases leads to end stage of renal disease (ESRD). This pathology is caused by mutations of either <i>PKD1</i> or <i>PKD2</i> genes that encode for polycystin-1 (PC1) and polycystin-2 (PC2), respectively. These proteins function as receptor-channel complex able to regulate calcium homeostasis. <i>PKD1</i>/<i>2</i> loss of function impairs different signalling pathways including cAMP and mTOR that are considered therapeutic targets for this disease. In fact, Tolvaptan, a vasopressin-2 antagonist that reduces cAMP levels, is the only drug approved for ADPKD treatment. Nevertheless, some ADPKD patients developed side effects in response to Tolvaptan including liver damage. Conversely, mTOR inhibitors that induced disease regression in ADPKD animal models failed the clinical trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Here, we show that the inhibition of mTOR causes the activation of autophagy in ADPKD cells that could reduce therapy effectiveness by drug degradation through the autophagic vesicles. Consistently, the combined treatment with rapamycin and chloroquine, an autophagy inhibitor, potentiates the decrease of cell proliferation induced by rapamycin. To overcome the dangerous activation of autophagy by mTOR inhibition, we targeted MDM2 (a downstream effector of mTOR signalling) that is involved in TP53 degradation by using RG7112, a small-molecule MDM2 inhibitor used for the treatment of haematologic malignancies. The inhibition of MDM2 by RG7112 prevents TP53 degradation and increases p21 expression leading to the decrease of cell proliferation and the activation of apoptosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The targeting of MDM2 by RG7112 might represent a new therapeutic option for the treatment of ADPKD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"115 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2022-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.202200037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10478156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromatin epigenetics and nuclear lamina keep the nucleus in shape: Examples from natural and accelerated aging","authors":"Pietro Salvatore Carollo,&nbsp;Viviana Barra","doi":"10.1111/boc.202200023","DOIUrl":"10.1111/boc.202200023","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <p>As the repository of genetic information, the cell nucleus must protect DNA integrity from mechanical stresses. The nuclear lamina, which resides within the nuclear envelope (NE), is made up of lamins, intermediate filaments bound to DNA. The nuclear lamina provides the nucleus with the ability to deal with inward as well as outward mechanical stimuli. Chromatin, in turn, through its degrees of compaction, shares this role with the nuclear lamina, thus, ensuring the plasticity of the nucleus. Perturbation of chromatin condensation or the nuclear lamina has been linked to a plethora of biological conditions, that range from cancer and genetic diseases (laminopathies) to aging, both natural and accelerated, such as the case of Hutchinson-Gilford Progeria Syndrome (HGPS). From the experimental results accumulated so far on the topic, a direct link between variations of the epigenetic pattern and nuclear lamina structure would be suggested, however, it has never been clarified thoroughly. This relationship, instead, has a downstream important implication on nucleus shape, genome preservation, force sensing, and, ultimately, aging-related disease onset. With this review, we aim to collect recent studies on the importance of both nuclear lamina components and chromatin status in nuclear mechanics. We also aim to bring to light evidence of the link between DNA methylation and nuclear lamina in natural and accelerated aging.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"115 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2022-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/boc.202200023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10486196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}