Pub Date : 2024-09-27eCollection Date: 2024-01-01DOI: 10.3389/fcell.2024.1492867
Ming-Chuan Hsu
{"title":"Editorial: Breakthroughs in tumor stem cell research.","authors":"Ming-Chuan Hsu","doi":"10.3389/fcell.2024.1492867","DOIUrl":"https://doi.org/10.3389/fcell.2024.1492867","url":null,"abstract":"","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-27eCollection Date: 2024-01-01DOI: 10.3389/fcell.2024.1493626
F Pagliari, S Di Franco, L Tirinato
{"title":"Editorial: Lipid alterations in cancer development, resistance and recurrence.","authors":"F Pagliari, S Di Franco, L Tirinato","doi":"10.3389/fcell.2024.1493626","DOIUrl":"https://doi.org/10.3389/fcell.2024.1493626","url":null,"abstract":"","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-27eCollection Date: 2024-01-01DOI: 10.3389/fcell.2024.1451274
Travis H Stracker
The transcription factor p53 (encoded by TP53) plays diverse roles in human development and disease. While best known for its role in tumor suppression, p53 signaling also influences mammalian development by triggering cell fate decisions in response to a wide variety of stresses. After over 4 decades of study, a new pathway that triggers p53 activation in response to mitotic delays was recently identified. Termed the mitotic surveillance or mitotic stopwatch pathway, the USP28 and 53BP1 proteins activate p53 in response to delayed mitotic progression to control cell fate and promote genomic stability. In this Minireview, I discuss its identification, potential roles in neurodevelopmental disorders and cancer, as well as explore outstanding questions about its function, regulation and potential use as a biomarker for anti-mitotic therapies.
{"title":"Regulation of p53 by the mitotic surveillance/stopwatch pathway: implications in neurodevelopment and cancer.","authors":"Travis H Stracker","doi":"10.3389/fcell.2024.1451274","DOIUrl":"https://doi.org/10.3389/fcell.2024.1451274","url":null,"abstract":"<p><p>The transcription factor p53 (encoded by <i>TP53</i>) plays diverse roles in human development and disease. While best known for its role in tumor suppression, p53 signaling also influences mammalian development by triggering cell fate decisions in response to a wide variety of stresses. After over 4 decades of study, a new pathway that triggers p53 activation in response to mitotic delays was recently identified. Termed the mitotic surveillance or mitotic stopwatch pathway, the USP28 and 53BP1 proteins activate p53 in response to delayed mitotic progression to control cell fate and promote genomic stability. In this Minireview, I discuss its identification, potential roles in neurodevelopmental disorders and cancer, as well as explore outstanding questions about its function, regulation and potential use as a biomarker for anti-mitotic therapies.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-27eCollection Date: 2024-01-01DOI: 10.3389/fcell.2024.1483345
John H Henson, Gabriela Reyes, Nina T Lo, Karina Herrera, Quenelle W McKim, Hannah Y Herzon, Maritriny Galvez-Ceron, Alexandra E Hershey, Rachael S Kim, Charles B Shuster
Our knowledge of the assembly and dynamics of the cytokinetic contractile ring (CR) in animal cells remains incomplete. We have previously used super-resolution light microscopy and platinum replica electron microscopy to elucidate the ultrastructural organization of the CR in first division sea urchin embryos. To date, our studies indicate that the CR initiates as an equatorial band of clusters containing myosin II, actin, septin and anillin, which then congress over time into patches which coalesce into a linear array characteristic of mature CRs. In the present study, we applied super-resolution interferometric photoactivated localization microscopy to confirm the existence of septin filament-like structures in the developing CR, demonstrate the close associations between septin2, anillin, and myosin II in the CR, as well as to show that septin2 appears consistently submembranous, whereas anillin is more widely distributed in the early CR. We also provide evidence that the major actin cross-linking protein α-actinin only associates with the linearized, late-stage CR and not with the early CR clusters, providing further support to the idea that α-actinin associates with actomyosin structures under tension and can serve as a counterbalance. In addition, we show that inhibition of actomyosin contraction does not stop the assembly of the early CR clusters but does arrest the progression of these structures to the aligned arrays required for functional cytokinesis. Taken together our results reinforce and extend our model for a cluster to patch to linear structural progression of the CR in sea urchin embryos and highlight the evolutionary relationships with cytokinesis in fission yeast.
{"title":"Cytokinetic contractile ring structural progression in an early embryo: positioning of scaffolding proteins, recruitment of α-actinin, and effects of myosin II inhibition.","authors":"John H Henson, Gabriela Reyes, Nina T Lo, Karina Herrera, Quenelle W McKim, Hannah Y Herzon, Maritriny Galvez-Ceron, Alexandra E Hershey, Rachael S Kim, Charles B Shuster","doi":"10.3389/fcell.2024.1483345","DOIUrl":"https://doi.org/10.3389/fcell.2024.1483345","url":null,"abstract":"<p><p>Our knowledge of the assembly and dynamics of the cytokinetic contractile ring (CR) in animal cells remains incomplete. We have previously used super-resolution light microscopy and platinum replica electron microscopy to elucidate the ultrastructural organization of the CR in first division sea urchin embryos. To date, our studies indicate that the CR initiates as an equatorial band of clusters containing myosin II, actin, septin and anillin, which then congress over time into patches which coalesce into a linear array characteristic of mature CRs. In the present study, we applied super-resolution interferometric photoactivated localization microscopy to confirm the existence of septin filament-like structures in the developing CR, demonstrate the close associations between septin2, anillin, and myosin II in the CR, as well as to show that septin2 appears consistently submembranous, whereas anillin is more widely distributed in the early CR. We also provide evidence that the major actin cross-linking protein α-actinin only associates with the linearized, late-stage CR and not with the early CR clusters, providing further support to the idea that α-actinin associates with actomyosin structures under tension and can serve as a counterbalance. In addition, we show that inhibition of actomyosin contraction does not stop the assembly of the early CR clusters but does arrest the progression of these structures to the aligned arrays required for functional cytokinesis. Taken together our results reinforce and extend our model for a cluster to patch to linear structural progression of the CR in sea urchin embryos and highlight the evolutionary relationships with cytokinesis in fission yeast.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-26eCollection Date: 2024-01-01DOI: 10.3389/fcell.2024.1477173
Masataka Kunii, Akihiro Harada
Cell polarity is essential for cellular function. Directional transport within a cell is called polarized transport, and it plays an important role in cell polarity. In this review, we will introduce the molecular mechanisms of polarized transport, particularly apical transport, and its physiological importance.
{"title":"Molecular mechanisms of polarized transport to the apical plasma membrane.","authors":"Masataka Kunii, Akihiro Harada","doi":"10.3389/fcell.2024.1477173","DOIUrl":"https://doi.org/10.3389/fcell.2024.1477173","url":null,"abstract":"<p><p>Cell polarity is essential for cellular function. Directional transport within a cell is called polarized transport, and it plays an important role in cell polarity. In this review, we will introduce the molecular mechanisms of polarized transport, particularly apical transport, and its physiological importance.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11497131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-26eCollection Date: 2024-01-01DOI: 10.3389/fcell.2024.1361485
Shujuan Li, Quan Zou, Yao Jiang, Yi Wang, Xiangdong Ding
Introduction: The hair follicle (HF) is a micro-organ capable of regeneration. A HF cycle consists of an anagen, catagen and telogen. Abnormalities in the HF cycle can lead to many hair disorders such as hair loss. The pig is a good biomedical model, but there are few data on their HF cycle. The aim of this study was to classify the pig HF cycle and determine the feasibility of the pig as an animal model for human HF cycle.
Methods: Skin samples from 10 different postnatal (P) days Yorkshire pigs was collected to determine the key time points of the first HF cycle in pig by H&E staining, immunofluorescence staining, q-PCR and western-blot.
Results: By morphological observation and detection of markers at different stages, pig HF cycle was classified into three main periods - the first anagen until P45, catagen (P45-P85), telogen (P85-P100), and next anagen (>P100). In addition, we examined the expression of important genes AE15, CD34, Versican, Ki67 et al. related to the HF cycle at different stages of pig HF, indicating that pig and human share similarities in morphology and marker gene expression patterns of HF cycle.
Discussion: Our findings will facilitate the study of HF cycle and offer researchers a suitable model for human hair research.
{"title":"A pig model exploring the postnatal hair follicle cycle.","authors":"Shujuan Li, Quan Zou, Yao Jiang, Yi Wang, Xiangdong Ding","doi":"10.3389/fcell.2024.1361485","DOIUrl":"10.3389/fcell.2024.1361485","url":null,"abstract":"<p><strong>Introduction: </strong>The hair follicle (HF) is a micro-organ capable of regeneration. A HF cycle consists of an anagen, catagen and telogen. Abnormalities in the HF cycle can lead to many hair disorders such as hair loss. The pig is a good biomedical model, but there are few data on their HF cycle. The aim of this study was to classify the pig HF cycle and determine the feasibility of the pig as an animal model for human HF cycle.</p><p><strong>Methods: </strong>Skin samples from 10 different postnatal (P) days Yorkshire pigs was collected to determine the key time points of the first HF cycle in pig by H&E staining, immunofluorescence staining, q-PCR and western-blot.</p><p><strong>Results: </strong>By morphological observation and detection of markers at different stages, pig HF cycle was classified into three main periods - the first anagen until P45, catagen (P45-P85), telogen (P85-P100), and next anagen (>P100). In addition, we examined the expression of important genes <i>AE15</i>, <i>CD34</i>, <i>Versican</i>, <i>Ki67</i> et al. related to the HF cycle at different stages of pig HF, indicating that pig and human share similarities in morphology and marker gene expression patterns of HF cycle.</p><p><strong>Discussion: </strong>Our findings will facilitate the study of HF cycle and offer researchers a suitable model for human hair research.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-26eCollection Date: 2024-01-01DOI: 10.3389/fcell.2024.1447939
Penghui Li, Yuan Xue
Recent advances in high-resolution mass spectrometry-based proteomics have improved our understanding of lysine acetylation in proteins, including histones and non-histone proteins. Lysine acetylation, a reversible post-translational modification, is catalyzed by lysine acetyltransferases (KATs) and lysine deacetylases (KDACs). Proteins comprising evolutionarily conserved bromodomains (BRDs) recognize these acetylated lysine residues and consequently activate transcription. Lysine acetylation regulates almost all cellular processes, including transcription, cell cycle progression, and metabolic functions. Studies have reported the aberrant expression, translocation, and mutation of genes encoding lysine acetylation regulators in various cancers, including digestive tract cancers. These dysregulated lysine acetylation regulators contribute to the pathogenesis of digestive system cancers by modulating the expression and activity of cancer-related genes or pathways. Several inhibitors targeting KATs, KDACs, and BRDs are currently in preclinical trials and have demonstrated anti-cancer effects. Digestive tract cancers, including encompass esophageal, gastric, colorectal, liver, and pancreatic cancers, represent a group of heterogeneous malignancies. However, these cancers are typically diagnosed at an advanced stage owing to the lack of early symptoms and are consequently associated with poor 5-year survival rates. Thus, there is an urgent need to identify novel biomarkers for early detection, as well as to accurately predict the clinical outcomes and identify effective therapeutic targets for these malignancies. Although the role of lysine acetylation in digestive tract cancers remains unclear, further analysis could improve our understanding of its role in the pathogenesis of digestive tract cancers. This review aims to summarize the implications and pathogenic mechanisms of lysine acetylation dysregulation in digestive tract cancers, as well as its potential clinical applications.
{"title":"Dysregulation of lysine acetylation in the pathogenesis of digestive tract cancers and its clinical applications.","authors":"Penghui Li, Yuan Xue","doi":"10.3389/fcell.2024.1447939","DOIUrl":"10.3389/fcell.2024.1447939","url":null,"abstract":"<p><p>Recent advances in high-resolution mass spectrometry-based proteomics have improved our understanding of lysine acetylation in proteins, including histones and non-histone proteins. Lysine acetylation, a reversible post-translational modification, is catalyzed by lysine acetyltransferases (KATs) and lysine deacetylases (KDACs). Proteins comprising evolutionarily conserved bromodomains (BRDs) recognize these acetylated lysine residues and consequently activate transcription. Lysine acetylation regulates almost all cellular processes, including transcription, cell cycle progression, and metabolic functions. Studies have reported the aberrant expression, translocation, and mutation of genes encoding lysine acetylation regulators in various cancers, including digestive tract cancers. These dysregulated lysine acetylation regulators contribute to the pathogenesis of digestive system cancers by modulating the expression and activity of cancer-related genes or pathways. Several inhibitors targeting KATs, KDACs, and BRDs are currently in preclinical trials and have demonstrated anti-cancer effects. Digestive tract cancers, including encompass esophageal, gastric, colorectal, liver, and pancreatic cancers, represent a group of heterogeneous malignancies. However, these cancers are typically diagnosed at an advanced stage owing to the lack of early symptoms and are consequently associated with poor 5-year survival rates. Thus, there is an urgent need to identify novel biomarkers for early detection, as well as to accurately predict the clinical outcomes and identify effective therapeutic targets for these malignancies. Although the role of lysine acetylation in digestive tract cancers remains unclear, further analysis could improve our understanding of its role in the pathogenesis of digestive tract cancers. This review aims to summarize the implications and pathogenic mechanisms of lysine acetylation dysregulation in digestive tract cancers, as well as its potential clinical applications.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-25eCollection Date: 2024-01-01DOI: 10.3389/fcell.2024.1459183
Xiaodi Huang, Mengyi Lian, Changzhong Li
Copper (Cu) is an essential trace element involved in a variety of biological processes, such as antioxidant defense, mitochondrial respiration, and bio-compound synthesis. In recent years, a novel theory called cuproptosis has emerged to explain how Cu induces programmed cell death. Cu targets lipoylated enzymes in the tricarboxylic acid cycle and subsequently triggers the oligomerization of lipoylated dihydrolipoamide S-acetyltransferase, leading to the loss of Fe-S clusters and induction of heat shock protein 70. Gynecological malignancies including cervical cancer, ovarian cancer and uterine corpus endometrial carcinoma significantly impact women's quality of life and even pose a threat to their lives. Excessive Cu can promote cancer progression by enhancing tumor growth, proliferation, angiogenesis and metastasis through multiple signaling pathways. However, there are few studies investigating gynecological cancers in relation to cuproptosis. Therefore, this review discusses Cu homeostasis and cuproptosis while exploring the potential use of cuproptosis for prognosis prediction as well as its implications in the progression and treatment of gynecological cancers. Additionally, we explore the application of Cu ionophore therapy in treating gynecological malignancies.
铜(Cu)是一种重要的微量元素,参与多种生物过程,如抗氧化防御、线粒体呼吸和生物化合物合成。近年来,一种名为 "杯突症"(cuproptosis)的新理论出现,用以解释铜如何诱导细胞程序性死亡。铜以三羧酸循环中的脂酰化酶为目标,随后引发脂酰化二氢脂酰胺 S-乙酰转移酶的寡聚化,导致 Fe-S 簇的丧失和热休克蛋白 70 的诱导。包括宫颈癌、卵巢癌和子宫内膜癌在内的妇科恶性肿瘤严重影响妇女的生活质量,甚至对她们的生命构成威胁。过量的 Cu 可通过多种信号通路促进肿瘤生长、增殖、血管生成和转移,从而促进癌症进展。然而,很少有研究调查妇科癌症与铜中毒的关系。因此,这篇综述讨论了铜稳态和铜突变,同时探讨了铜突变在预后预测中的潜在用途及其在妇科癌症进展和治疗中的意义。此外,我们还探讨了治疗妇科恶性肿瘤中Cu离子团疗法的应用。
{"title":"Copper homeostasis and cuproptosis in gynecological cancers.","authors":"Xiaodi Huang, Mengyi Lian, Changzhong Li","doi":"10.3389/fcell.2024.1459183","DOIUrl":"10.3389/fcell.2024.1459183","url":null,"abstract":"<p><p>Copper (Cu) is an essential trace element involved in a variety of biological processes, such as antioxidant defense, mitochondrial respiration, and bio-compound synthesis. In recent years, a novel theory called cuproptosis has emerged to explain how Cu induces programmed cell death. Cu targets lipoylated enzymes in the tricarboxylic acid cycle and subsequently triggers the oligomerization of lipoylated dihydrolipoamide S-acetyltransferase, leading to the loss of Fe-S clusters and induction of heat shock protein 70. Gynecological malignancies including cervical cancer, ovarian cancer and uterine corpus endometrial carcinoma significantly impact women's quality of life and even pose a threat to their lives. Excessive Cu can promote cancer progression by enhancing tumor growth, proliferation, angiogenesis and metastasis through multiple signaling pathways. However, there are few studies investigating gynecological cancers in relation to cuproptosis. Therefore, this review discusses Cu homeostasis and cuproptosis while exploring the potential use of cuproptosis for prognosis prediction as well as its implications in the progression and treatment of gynecological cancers. Additionally, we explore the application of Cu ionophore therapy in treating gynecological malignancies.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-25eCollection Date: 2024-01-01DOI: 10.3389/fcell.2024.1455280
Cecilia S Blengini, Karen Schindler
The Aurora Kinases (AURKs) are a family of serine-threonine protein kinases critical for cell division. Somatic cells express only AURKA and AURKB. However, mammalian germ cells and some cancer cells express all three isoforms. A major question in the field has been determining the molecular and cellular changes when cells express three instead of two aurora kinases. Using a systematic genetic approach involving different Aurora kinase oocyte-specific knockout combinations, we completed an oocyte-AURK genetic interaction map and show that one genomic copy of Aurka is necessary and sufficient to support female fertility and oocyte meiosis. We further confirm that AURKB and AURKC alone cannot compensate for AURKA. These results highlight the importance of AURKA in mouse oocytes, demonstrating that it is required for spindle formation and proper chromosome segregation. Surprisingly, a percentage of oocytes that lack AURKB can complete meiosis I, but the quality of those eggs is compromised, suggesting a role in AURKB to regulate spindle assembly checkpoint or control the cell cycle. Together with our previous studies, we wholly define the genetic interplay among the Aurora kinases and reinforce the importance of AURKA expression in oocyte meiosis.
极光激酶(AURKs)是丝氨酸-苏氨酸蛋白激酶家族中对细胞分裂至关重要的一种。体细胞只表达 AURKA 和 AURKB。然而,哺乳动物生殖细胞和一些癌细胞则表达所有三种同工酶。该领域的一个主要问题是确定当细胞表达三种而不是两种极光激酶时分子和细胞的变化。我们采用了一种涉及不同极光激酶卵母细胞特异性基因敲除组合的系统遗传方法,完成了卵母细胞-极光激酶基因相互作用图谱,并表明一个极光激酶基因组拷贝对于支持雌性生育能力和卵母细胞减数分裂是必要且足够的。我们进一步证实,AURKB 和 AURKC 无法单独补偿 AURKA。这些结果突显了 AURKA 在小鼠卵母细胞中的重要性,证明它是纺锤体形成和染色体正常分离所必需的。令人惊讶的是,一部分缺乏AURKB的卵母细胞可以完成减数分裂I,但这些卵子的质量却受到了影响,这表明AURKB在调节纺锤体组装检查点或控制细胞周期方面发挥作用。结合之前的研究,我们完全确定了极光激酶之间的遗传相互作用,并强化了AURKA表达在卵母细胞减数分裂中的重要性。
{"title":"Genetic interaction mapping of Aurora protein kinases in mouse oocytes.","authors":"Cecilia S Blengini, Karen Schindler","doi":"10.3389/fcell.2024.1455280","DOIUrl":"10.3389/fcell.2024.1455280","url":null,"abstract":"<p><p>The Aurora Kinases (AURKs) are a family of serine-threonine protein kinases critical for cell division. Somatic cells express only AURKA and AURKB. However, mammalian germ cells and some cancer cells express all three isoforms. A major question in the field has been determining the molecular and cellular changes when cells express three instead of two aurora kinases. Using a systematic genetic approach involving different Aurora kinase oocyte-specific knockout combinations, we completed an oocyte-AURK genetic interaction map and show that one genomic copy of <i>Aurka</i> is necessary and sufficient to support female fertility and oocyte meiosis. We further confirm that AURKB and AURKC alone cannot compensate for AURKA. These results highlight the importance of AURKA in mouse oocytes, demonstrating that it is required for spindle formation and proper chromosome segregation. Surprisingly, a percentage of oocytes that lack AURKB can complete meiosis I, but the quality of those eggs is compromised, suggesting a role in AURKB to regulate spindle assembly checkpoint or control the cell cycle. Together with our previous studies, we wholly define the genetic interplay among the Aurora kinases and reinforce the importance of AURKA expression in oocyte meiosis.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-24eCollection Date: 2024-01-01DOI: 10.3389/fcell.2024.1466915
Rico Gamuyao, Chi-Lun Chang
Organelle contact sites are regions where two heterologous membranes are juxtaposed by molecular tethering complexes. These contact sites are important in inter-organelle communication and cellular functional integration. However, visualizing these minute foci and identifying contact site proteomes have been challenging. In recent years, fluorescence-based methods have been developed to visualize the dynamic physical interaction of organelles while proximity labeling approaches facilitate the profiling of proteomes at contact sites. In this review, we explain the design principle for these contact site reporters: a dual-organelle interaction mechanism based on how endogenous tethers and/or tethering complexes localize to contact sites. We classify the contact site reporters into three categories: (i) single-protein systems, (ii) two-component systems with activated reporter signal upon organelle proximity, and (iii) reporters for contact site proteomes. We also highlight advanced imaging analysis with high temporal-spatial resolution and the use of machine-learning algorithms for detecting contact sites.
{"title":"Imaging and proteomics toolkits for studying organelle contact sites.","authors":"Rico Gamuyao, Chi-Lun Chang","doi":"10.3389/fcell.2024.1466915","DOIUrl":"https://doi.org/10.3389/fcell.2024.1466915","url":null,"abstract":"<p><p>Organelle contact sites are regions where two heterologous membranes are juxtaposed by molecular tethering complexes. These contact sites are important in inter-organelle communication and cellular functional integration. However, visualizing these minute foci and identifying contact site proteomes have been challenging. In recent years, fluorescence-based methods have been developed to visualize the dynamic physical interaction of organelles while proximity labeling approaches facilitate the profiling of proteomes at contact sites. In this review, we explain the design principle for these contact site reporters: a dual-organelle interaction mechanism based on how endogenous tethers and/or tethering complexes localize to contact sites. We classify the contact site reporters into three categories: (i) single-protein systems, (ii) two-component systems with activated reporter signal upon organelle proximity, and (iii) reporters for contact site proteomes. We also highlight advanced imaging analysis with high temporal-spatial resolution and the use of machine-learning algorithms for detecting contact sites.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}