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Axon demyelination and degeneration in a zebrafish spastizin model of hereditary spastic paraplegia. 遗传性痉挛性截瘫斑马鱼痉挛素模型中的轴突脱髓鞘和退化。
IF 4.5 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-11-06 DOI: 10.1098/rsob.240100
Vranda Garg, Selina André, Luisa Heyer, Gudrun Kracht, Torben Ruhwedel, Patricia Scholz, Till Ischebeck, Hauke B Werner, Christian Dullin, Jacob Engelmann, Wiebke Möbius, Martin C Göpfert, Roland Dosch, Bart R H Geurten

Hereditary spastic paraplegias (HSPs) are a diverse set of neurological disorders characterized by progressive spasticity and weakness in the lower limbs caused by damage to the axons of the corticospinal tract. More than 88 genetic mutations have been associated with HSP, yet the mechanisms underlying these disorders are not well understood. We replicated the pathophysiology of one form of HSP known as spastic paraplegia 15 (SPG15) in zebrafish. This disorder is caused in humans by mutations in the ZFYVE26 gene, which codes for a protein called SPASTIZIN. We show that, in zebrafish, the significant reduction of Spastizin caused degeneration of large motor neurons. Motor neuron degeneration is associated with axon demyelination in the spinal cord and impaired locomotion in the spastizin mutants. Our findings reveal that the reduction in Spastizin compromises axonal integrity and affects the myelin sheath, ultimately recapitulating the pathophysiology of HSPs.

遗传性痉挛性截瘫(HSP)是一种多种神经系统疾病,其特征是由于皮质脊髓束轴突受损而导致下肢进行性痉挛和无力。与 HSP 相关的基因突变超过 88 种,但这些疾病的发病机制尚不十分清楚。我们在斑马鱼身上复制了一种被称为痉挛性截瘫 15(SPG15)的 HSP 的病理生理学。这种疾病是由 ZFYVE26 基因突变引起的,该基因编码一种名为 SPASTIZIN 的蛋白质。我们的研究表明,在斑马鱼体内,Spastizin 的显著减少会导致大运动神经元退化。运动神经元变性与脊髓轴突脱髓鞘和 spastizin 突变体的运动障碍有关。我们的研究结果表明,Spastizin的减少会损害轴突的完整性并影响髓鞘,最终重现HSPs的病理生理学。
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引用次数: 0
Cebpa is required for haematopoietic stem and progenitor cell generation and maintenance in zebrafish. 斑马鱼造血干细胞和祖细胞的生成和维持需要 Cebpa。
IF 4.5 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-11-06 DOI: 10.1098/rsob.240215
Kemin Chen, Jieyi Wu, Yuxian Zhang, Wei Liu, Xiaohui Chen, Wenqing Zhang, Zhibin Huang

The CCAAT enhancer binding protein alpha (CEBPA) is crucial for myeloid differentiation and the balance of haematopoietic stem and progenitor cell (HSPC) quiescence and self-renewal, and its dysfunction can drive leukemogenesis. However, its role in HSPC generation has not been fully elucidated. Here, we utilized various zebrafish cebpa mutants to investigate the function of Cebpa in the HSPC compartment. Co-localization analysis showed that cebpa expression is enriched in nascent HSPCs. Complete loss of Cebpa function resulted in a significant reduction in early HSPC generation and the overall HSPC pool during embryonic haematopoiesis. Interestingly, while myeloid differentiation was impaired in cebpa N-terminal mutants expressing the truncated zP30 protein, the number of HSPCs was not affected, indicating a redundant role of Cebpa P42 and P30 isoforms in HSPC development. Additionally, epistasis experiments confirmed that Cebpa functions downstream of Runx1 to regulate HSPC emergence. Our findings uncover a novel role of Cebpa isoforms in HSPC generation and maintenance, and provide new insights into HSPC development.

CCAAT增强子结合蛋白α(CEBPA)对于髓系分化以及造血干细胞和祖细胞(HSPC)的静止和自我更新的平衡至关重要,其功能障碍可导致白血病的发生。然而,它在 HSPC 生成中的作用尚未完全阐明。在这里,我们利用各种斑马鱼 cebpa 突变体来研究 Cebpa 在 HSPC 区系中的功能。共定位分析表明,cebpa的表达富集在新生的HSPC中。Cebpa 功能的完全丧失导致胚胎造血过程中早期 HSPC 的生成和整个 HSPC 池的显著减少。有趣的是,在表达截短的 zP30 蛋白的 cebpa N 端突变体中,虽然髓系分化受损,但 HSPC 的数量却不受影响,这表明 Cebpa P42 和 P30 同工酶在 HSPC 发育中起着多余的作用。此外,外显子实验证实,Cebpa 在 Runx1 的下游发挥作用,调控 HSPC 的出现。我们的发现揭示了 Cebpa 同工酶在 HSPC 生成和维持中的新作用,并为 HSPC 的发育提供了新的见解。
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引用次数: 0
SID-2 is a conserved extracellular vesicle protein that is not associated with environmental RNAi in parasitic nematodes. SID-2 是一种保守的细胞外囊泡蛋白,与寄生线虫的环境 RNAi 无关。
IF 4.5 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-11-06 DOI: 10.1098/rsob.240190
Frances Blow, Kate Jeffrey, Franklin Wang-Ngai Chow, Inna A Nikonorova, Maureen M Barr, Atlanta G Cook, Bram Prevo, Dhanya K Cheerambathur, Amy H Buck

In the free-living nematode Caenorhabditis elegans, the transmembrane protein SID-2 imports double-stranded RNA into intestinal cells to trigger systemic RNA interference (RNAi), allowing organisms to sense and respond to environmental cues such as the presence of pathogens. This process, known as environmental RNAi, has not been observed in the most closely related parasites that are also within clade V. Previous sequence-based searches failed to identify sid-2 orthologues in available clade V parasite genomes. In this study, we identified sid-2 orthologues in these parasites using genome synteny and protein structure-based comparison, following identification of a SID-2 orthologue in extracellular vesicles from the murine intestinal parasitic nematode Heligmosomoides bakeri. Expression of GFP-tagged H. bakeri SID-2 in C. elegans showed similar localization to the intestinal apical membrane as seen for GFP-tagged C. elegans SID-2, and further showed mobility in intestinal cells in vesicle-like structures. We tested the capacity of H. bakeri SID-2 to functionally complement environmental RNAi in a C. elegans SID-2 null mutant and show that H. bakeri SID-2 does not rescue the phenotype in this context. Our work identifies SID-2 as a highly abundant EV protein whose ancestral function may be unrelated to environmental RNAi, and rather highlights an association with extracellular vesicles in nematodes.

在自由生活的线虫秀丽隐杆线虫(Caenorhabditis elegans)中,跨膜蛋白SID-2将双链RNA导入肠细胞,引发系统性RNA干扰(RNAi),使生物体能够感知环境线索(如病原体的存在)并做出反应。这一过程被称为环境 RNAi,但在同属 V 支系的关系最密切的寄生虫中却未观察到这一过程。在本研究中,我们利用基因组同源性和基于蛋白质结构的比较,在小鼠肠道寄生线虫 Heligmosomoides bakeri 的细胞外囊泡中发现了 SID-2 的同源物,从而确定了这些寄生虫中的 sid-2 同源物。在 elegans 中表达 GFP 标记的 H. bakeri SID-2,显示出与 GFP 标记的 C. elegans SID-2 相似的在肠顶端膜的定位,并进一步显示出在肠细胞中囊泡状结构的流动性。我们测试了H. bakeri SID-2对 elegans SID-2缺失突变体中环境RNAi的功能补充能力,结果表明H. bakeri SID-2并不能在这种情况下挽救表型。我们的研究发现,SID-2是一种高含量的EV蛋白,其祖先的功能可能与环境RNAi无关,而是强调了它与线虫细胞外囊泡的联系。
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引用次数: 0
Cell cycle visualization tools to study cardiomyocyte proliferation in real-time. 用于实时研究心肌细胞增殖的细胞周期可视化工具。
IF 4.5 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-10-09 DOI: 10.1098/rsob.240167
Rustem Salmenov, Christine Mummery, Menno Ter Huurne

Cardiomyocytes in the adult human heart are quiescent and those lost following heart injury are not replaced by proliferating survivors. Considerable effort has been made to understand the mechanisms underlying cardiomyocyte cell cycle exit and re-entry, with view to discovering therapeutics that could stimulate cardiomyocyte proliferation and heart regeneration. The advent of large compound libraries and robotic liquid handling platforms has enabled the screening of thousands of conditions in a single experiment but success of these screens depends on the appropriateness and quality of the model used. Quantification of (human) cardiomyocyte proliferation in high throughput has remained problematic because conventional antibody-based staining is costly, technically challenging and does not discriminate between cardiomyocyte division and failure in karyokinesis or cytokinesis. Live cell imaging has provided alternatives that facilitate high-throughput screening but these have other limitations. Here, we (i) review the cell cycle features of cardiomyocytes, (ii) discuss various cell cycle fluorescent reporter systems, and (iii) speculate on what could improve their predictive value in the context of cardiomyocyte proliferation. Finally, we consider how these new methods can be used in combination with state-of-the-art three-dimensional human cardiac organoid platforms to identify pro-proliferative signalling pathways that could stimulate regeneration of the human heart.

成人心脏中的心肌细胞处于静止状态,心脏损伤后失去的心肌细胞不会被增殖的幸存者取代。为了了解心肌细胞细胞周期的退出和再进入机制,发现能刺激心肌细胞增殖和心脏再生的治疗方法,人们付出了巨大的努力。大型化合物库和机器人液体处理平台的出现使得在一次实验中筛选数千种条件成为可能,但这些筛选的成功与否取决于所用模型的适当性和质量。高通量量化(人类)心肌细胞增殖仍然是个问题,因为传统的抗体染色成本高、技术难度大,而且不能区分心肌细胞分裂与核动或细胞分裂失败。活细胞成像技术为高通量筛选提供了替代方案,但也有其他局限性。在此,我们将(i) 回顾心肌细胞的细胞周期特征,(ii) 讨论各种细胞周期荧光报告系统,(iii) 推测在心肌细胞增殖的背景下如何提高它们的预测价值。最后,我们将考虑如何将这些新方法与最先进的三维人类心脏类器官平台结合使用,以确定可刺激人类心脏再生的促增殖信号通路。
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引用次数: 0
Moesin contributes to heat shock gene response through direct binding to the Med15 subunit of the Mediator complex in the nucleus. Moesin 通过与细胞核中 Mediator 复合物的 Med15 亚基直接结合,促进热休克基因的反应。
IF 4.5 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-10-02 DOI: 10.1098/rsob.240110
Ildikó Kristó, Zoltán Kovács, Anikó Szabó, Péter Borkúti, Alexandra Gráf, Ádám Tamás Sánta, Aladár Pettkó-Szandtner, Edit Ábrahám, Viktor Honti, Zoltán Lipinszki, Péter Vilmos

The members of the evolutionary conserved actin-binding Ezrin, Radixin and Moesin (ERM) protein family are involved in numerous key cellular processes in the cytoplasm. In the last decades, ERM proteins, like actin and other cytoskeletal components, have also been shown to be functional components of the nucleus; however, the molecular mechanism behind their nuclear activities remained unclear. Therefore, our primary aim was to identify the nuclear protein interactome of the single Drosophila ERM protein, Moesin. We demonstrate that Moesin directly interacts with the Mediator complex through direct binding to its Med15 subunit, and the presence of Moesin at the regulatory regions of the Hsp70Ab heat shock gene was found to be Med15-dependent. Both Moesin and Med15 bind to heat shock factor (Hsf), and they are required for proper Hsp gene expression under physiological conditions. Moreover, we confirmed that Moesin, Med15 and Hsf are able to bind the monomeric form of actin and together they form a complex in the nucleus. These results elucidate a mechanism by which ERMs function within the nucleus. Finally, we present the direct interaction of the human orthologues of Drosophila Moesin and Med15, which highlights the evolutionary significance of our finding.

进化保守的肌动蛋白结合型 Ezrin、Radixin 和 Moesin(ERM)蛋白家族成员参与了细胞质中许多关键的细胞过程。在过去的几十年中,ERM 蛋白与肌动蛋白和其他细胞骨架成分一样,也被证明是细胞核的功能成分;然而,其核活动背后的分子机制仍不清楚。因此,我们的主要目的是鉴定单一果蝇ERM蛋白Moesin的核蛋白相互作用组。我们证明,Moesin通过与Mediator复合物的Med15亚基直接结合而与Mediator复合物直接相互作用,并且发现Moesin存在于Hsp70Ab热休克基因的调控区域是依赖于Med15的。Moesin和Med15都与热休克因子(Hsf)结合,它们是生理条件下Hsp基因正常表达所必需的。此外,我们还证实,Moesin、Med15 和 Hsf 能够结合肌动蛋白的单体形式,并在细胞核中形成复合物。这些结果阐明了 ERMs 在细胞核内发挥作用的机制。最后,我们介绍了果蝇 Moesin 和 Med15 的人类直向同源物之间的直接相互作用,这凸显了我们的发现在进化方面的意义。
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引用次数: 0
Internal regulation between constitutively expressed T cell co-inhibitory receptors BTLA and CD5 and tolerance in recent thymic emigrants. 组成型表达的 T 细胞共抑制受体 BTLA 和 CD5 之间的内部调节与近期胸腺移居者的耐受性。
IF 4.5 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-10-30 DOI: 10.1098/rsob.240178
Adeolu O Adegoke, Govindarajan Thangavelu, Ting-Fang Chou, Marcos I Petersen, Kiyokazu Kakugawa, Julia F May, Kevin Joannou, Qingyang Wang, Kristofor K Ellestad, Louis Boon, Peter A Bretscher, Hilde Cheroutre, Mitchell Kronenberg, Troy A Baldwin, Colin C Anderson

Immunologic self-tolerance involves signals from co-inhibitory receptors. Several T cell co-inhibitors, including PD-1, are expressed upon activation, whereas CD5 and BTLA are expressed constitutively. The relationship between constitutively expressed co-inhibitors and when they are needed is unknown. Deletion of Btla demonstrated BTLA regulates CD5 expression. Loss of BTLA signals, but not signalling by its ligand, HVEM, leads to increased CD5 expression. Higher CD5 expression set during thymic selection is associated with increased self-recognition, suggesting that BTLA might be needed early to establish self-tolerance. We found that BTLA and PD-1 were needed post-thymic selection in recent thymic emigrants (RTE). RTE lacking BTLA caused a CD4 T cell and MHC class II dependent multi-organ autoimmune disease. Together, our findings identify a negative regulatory pathway between two constitutively expressed co-inhibitors, calibrating their expression. Expression of constitutive and induced co-inhibitory receptors is needed early to establish tolerance in the periphery for RTE.

免疫自我耐受涉及来自协同抑制受体的信号。包括 PD-1 在内的几种 T 细胞辅助抑制剂在活化时表达,而 CD5 和 BTLA 则是组成型表达。组成型表达的协同抑制剂与何时需要它们之间的关系尚不清楚。Btla 的缺失表明 BTLA 可调节 CD5 的表达。BTLA 信号的缺失(而非其配体 HVEM 的信号缺失)会导致 CD5 表达的增加。胸腺选择过程中CD5表达的升高与自我识别能力的增强有关,这表明BTLA可能需要在早期建立自我耐受。我们发现,近期胸腺移植物(RTE)在胸腺选择后也需要 BTLA 和 PD-1。缺乏 BTLA 的 RTE 会导致 CD4 T 细胞和 MHC II 类依赖性多器官自身免疫疾病。我们的研究结果共同确定了两种组成型表达协同抑制因子之间的负调控途径,从而校准了它们的表达。组成型和诱导型共抑制受体的表达需要尽早在外周建立对 RTE 的耐受。
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引用次数: 0
Sex as a biological variable in ageing: insights and perspectives on the molecular and cellular hallmarks. 性别作为老化过程中的一个生物变量:对分子和细胞特征的认识和展望。
IF 4.5 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-10-30 DOI: 10.1098/rsob.240177
José Héctor Gibrán Fritz García, Claudia Isabelle Keller Valsecchi, M Felicia Basilicata

Sex-specific differences in lifespan and ageing are observed in various species. In humans, women generally live longer but are frailer and suffer from different age-related diseases compared to men. The hallmarks of ageing, such as genomic instability, telomere attrition or loss of proteostasis, exhibit sex-specific patterns. Sex chromosomes and sex hormones, as well as the epigenetic regulation of the inactive X chromosome, have been shown to affect lifespan and age-related diseases. Here we review the current knowledge on the biological basis of sex-biased ageing. While our review is focused on humans, we also discuss examples of model organisms such as the mouse, fruit fly or the killifish. Understanding these molecular differences is crucial as the elderly population is expected to double worldwide by 2050, making sex-specific approaches in the diagnosis, treatment, therapeutic development and prevention of age-related diseases a pressing need.

不同物种的寿命和衰老存在性别差异。在人类中,与男性相比,女性一般寿命更长,但更虚弱,并患有不同的老年相关疾病。衰老的特征,如基因组不稳定性、端粒损耗或蛋白稳态丧失,都表现出性别特异性模式。性染色体和性激素以及非活性 X 染色体的表观遗传调控已被证明会影响寿命和与年龄相关的疾病。在此,我们回顾了目前有关性别老化生物学基础的知识。虽然我们的综述侧重于人类,但也讨论了小鼠、果蝇或鳉鱼等模式生物的例子。预计到 2050 年,全球老年人口将翻一番,因此了解这些分子差异至关重要,这使得在诊断、治疗、治疗方法开发和预防老年相关疾病方面迫切需要有性别特异性的方法。
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引用次数: 0
Tail-anchored membrane protein SLMAP3 is essential for targeting centrosomal proteins to the nuclear envelope in skeletal myogenesis. 在骨骼肌发生过程中,尾锚膜蛋白SLMAP3对于将中心体蛋白靶向到核包膜至关重要。
IF 4.5 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-10-09 DOI: 10.1098/rsob.240094
Ana Paula Dias, Taha Rehmani, Maysoon Salih, Balwant Tuana

The positioning and communication between the nucleus and centrosomes are essential in cell division, differentiation and tissue formation. During skeletal myogenesis, the nuclei become evenly spaced with the switch of the microtubule-organizing centre (MTOC) from the centrosome to the nuclear envelope (NE). We report that the tail-anchored sarcolemmal membrane associated protein 3 (SLMAP3), a component of the MTOC and NE, is crucial for myogenesis because its deletion in mice leads to a reduction in the NE-MTOC formation, mislocalization of the nuclei, dysregulation of the myogenic programme and abnormal embryonic myofibres. SLMAP3-/- myoblasts also displayed a similar disorganized distribution of nuclei with an aberrant NE-MTOC and defective myofibre formation and differentiation programming. We identified novel interactors of SLMAP3, including pericentrin, PCM1 (pericentriolar material 1), AKAP9 (A-kinase anchoring protein 9), kinesin-1 members Kif5B (kinesin family member 5B), KCL1 (kinesin light chain 1), KLC2 (kinesin light chain 2) and nuclear lamins, and observed that the distribution of centrosomal proteins at the NE together with Nesprin-1 was significantly altered by the loss of SLMAP3 in differentiating myoblasts. SLMAP3 is believed to negatively regulate Hippo signalling, but its loss was without impact on this pathway in developing muscle. These results reveal that SLMAP3 is essential for skeletal myogenesis through unique mechanisms involving the positioning of nuclei, NE-MTOC dynamics and gene programming.

细胞核和中心体之间的定位和交流在细胞分裂、分化和组织形成过程中至关重要。在骨骼肌发生过程中,随着微管组织中心(MTOC)从中心体转移到核包膜(NE),细胞核变得均匀分布。我们报告说,尾锚定肌小体膜相关蛋白3(SLMAP3)是MTOC和NE的组成部分,对肌形成至关重要,因为小鼠缺失SLMAP3会导致NE-MTOC形成减少、细胞核错位、肌形成程序失调和胚胎肌纤维异常。SLMAP3-/-肌母细胞也表现出类似的细胞核分布紊乱、NE-MTOC异常、肌纤维形成和分化程序缺陷。我们发现了 SLMAP3 的新型相互作用者,包括包心蛋白、PCM1(包心皮材料 1)、AKAP9(A 激酶锚定蛋白 9)、驱动蛋白-1 成员 Kif5B(驱动蛋白家族成员 5B)、KCL1(驱动蛋白轻链 1)、并观察到在分化的肌母细胞中,由于 SLMAP3 的缺失,中心体蛋白与 Nesprin-1 在 NE 上的分布发生了显著变化。SLMAP3被认为对Hippo信号有负面调节作用,但在发育中的肌肉中,SLMAP3的缺失对这一通路没有影响。这些结果表明,SLMAP3通过涉及细胞核定位、NE-MTOC动态和基因编程的独特机制,对骨骼肌的发生至关重要。
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引用次数: 0
SLMAP3 is crucial for organogenesis through mechanisms involving primary cilia formation. SLMAP3 通过涉及初级纤毛形成的机制对器官形成至关重要。
IF 4.5 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-10-17 DOI: 10.1098/rsob.240206
Ana Paula Dias, Taha Rehmani, Billi Dawn Applin, Maysoon Salih, Balwant Tuana

SLMAP3 is a constituent of the centrosome and is known to assemble with the striatin-interacting phosphatase and kinase (STRIPAK) complex, where it has been reported to repress Hippo signalling. The global knockout of SLMAP3 in mice results in embryonic/perinatal lethality and stunted growth without changes in the phosphorylation status of YAP. Diverse phenotypes present in the SLMAP3-/- embryos include reduced body axis, small and abnormal organs resembling defects in planar cell polarity (PCP) signalling, while also displaying the notable polycystic kidneys, a known manifestation of ciliopathies. Analysis of cell polarity in primary mouse embryonic fibroblasts (MEFs) including cell migration, orientation and mitotic spindle angle did not reveal any changes due to SLMAP3 loss in these cells, although the expression of DVL3 was significantly reduced. Furthermore, MEFs lacking FGFR1OP2 or STRN3, two other STRIPAK members, did not reveal any significant changes in any of these parameters either. Significant changes in the number of ciliated cells and primary cilium length in SLMAP3 and FGFR1OP2 deficient MEFs were evident, while a reduced primary cilium length was notable in chondrocytes of SLMAP3 deficient embryos. Our findings suggest that SLMAP3 is essential for mouse embryogenesis through novel mechanisms involving the primary cilium/PCP and protein stability independent of Hippo signalling.

SLMAP3 是中心体的组成成分,已知可与纹蛋白相互作用磷酸酶和激酶(STRIPAK)复合物组装在一起,据报道可抑制 Hippo 信号。在小鼠中全面敲除 SLMAP3 会导致胚胎/围产期死亡和生长迟缓,但 YAP 的磷酸化状态不会发生变化。SLMAP3-/-胚胎的表型多种多样,包括体轴缩短、器官小且异常,类似于平面细胞极性(PCP)信号缺陷,同时还表现出显著的多囊肾,这是纤毛虫病的一种已知表现形式。对原代小鼠胚胎成纤维细胞(MEFs)的细胞极性(包括细胞迁移、定向和有丝分裂纺锤体角度)进行分析后发现,这些细胞并没有因为 SLMAP3 的缺失而发生任何变化,但 DVL3 的表达却显著减少。此外,缺乏另外两种 STRIPAK 成员 FGFR1OP2 或 STRN3 的 MEF 也没有发现这些参数有任何显著变化。在 SLMAP3 和 FGFR1OP2 缺乏的 MEF 中,纤毛细胞数量和初级纤毛长度发生了明显变化,而在 SLMAP3 缺乏的胚胎软骨细胞中,初级纤毛长度明显减少。我们的研究结果表明,SLMAP3 通过涉及初级纤毛/PCP 和蛋白稳定性的新机制对小鼠胚胎发育至关重要,而这些机制与 Hippo 信号无关。
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引用次数: 0
A cryptic plastid and a novel mitochondrial plasmid in Leucomyxa plasmidifera gen. and sp. nov. (Ochrophyta) push the frontiers of organellar biology. Leucomyxa plasmidifera gen.
IF 4.5 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-10-30 DOI: 10.1098/rsob.240022
Dovilė Barcytė, Karin Jaške, Tomáš Pánek, Tatiana Yurchenko, Tereza Ševčíková, Anežka Eliášová, Marek Eliáš

Complete plastid loss seems to be very rare among secondarily non-photosynthetic eukaryotes. Leukarachnion sp. PRA-24, an amoeboid colourless protist related to the photosynthetic algal class Synchromophyceae (Ochrophyta), is a candidate for such a case based on a previous investigation by transmission electron microscopy. Here, we characterize this organism in further detail and describe it as Leucomyxa plasmidifera gen. et sp. nov., additionally demonstrating it is the first known representative of a broader clade of non-photosynthetic ochrophytes. We recovered its complete plastid genome, exhibiting a reduced gene set similar to plastomes of other non-photosynthetic ochrophytes, yet being even more extreme in sequence divergence. Identification of components of the plastid protein import machinery in the L. plasmidifera transcriptome assembly corroborated that the organism possesses a cryptic plastid organelle. According to our bioinformatic reconstruction, the plastid contains a unique combination of biosynthetic pathways producing haem, a folate precursor and tocotrienols. As another twist to its organellar biology, L. plasmidifera turned out to contain an unusual long insertion in its mitogenome related to a newly discovered mitochondrial plasmid exhibiting unprecedented features in terms of its size and coding capacity. Combined, our work uncovered further striking outcomes of the evolutionary course of semiautonomous organelles in protists.

在第二类非光合真核生物中,完全丧失质体的情况似乎非常罕见。根据之前的透射电子显微镜研究,Leukarachnion sp. PRA-24(一种与光合藻类同步叶绿藻(Ochrophyta)有关的无色变形原生生物)是这种情况的候选者。在这里,我们进一步详细描述了这种生物的特征,并将其描述为 Leucomyxa plasmidifera gen.我们恢复了其完整的质体基因组,发现其质体基因组与其他非光合水华藻的质体基因组相似,但在序列差异方面却更为极端。在L. plasmidifera转录组中鉴定出了质体蛋白质导入机制的组成部分,这证实了该生物拥有一个隐蔽的质体细胞器。根据我们的生物信息学重建,该质体包含一个生产血红素、叶酸前体和生育三烯酚的独特生物合成途径组合。作为其细胞器生物学的另一个转折,L. plasmidifera 的有丝分裂基因组中含有一个不寻常的长插入物,该插入物与新发现的线粒体质粒有关,在大小和编码能力方面表现出前所未有的特征。综上所述,我们的工作进一步揭示了半自主细胞器在原生生物进化过程中的惊人结果。
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引用次数: 0
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