Article
Cell Biology
Tian Tian, Lili Chen, Zhen Dou, Zhisen Yang, Xinjiao Gao, Xiao Yuan, Chengliang Wang, Ran Liu, Zuojun Shen, Ping Gui, Maikun Teng, Xianlei Meng, Donald L. Hill, Lin Li, Xuan Zhang, Xing Liu, Linfeng Sun, Jianye Zang, Xuebiao Yao
Summary: This study reveals the molecular basis of how human CCAN interacts with duplex DNA and its importance in accurate chromosome segregation through cryo-electron microscopy and functional analyses.
Article
Multidisciplinary Sciences
Qianhua Dong, Xue-lei Liu, Xiao-hui Wang, Yu Zhao, Yu-hang Chen, Fei Li
Summary: CENP-T interacts with Ccp1 to regulate centromere binding throughout the cell cycle, involving phosphorylation of a specific domain CIM. Competitive exclusion between Ccp1 and Ndc80 at the N terminus of CENP-T via phosphorylation ensures precise kinetochore assembly during mitosis, uncovering a previously unrecognized mechanism for kinetochore assembly through the cell cycle.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Deniz Dogan, Merve Arslan, Tugce Ulucay, Sibel Kalyoncu, Stefan Dimitrov, Seyit Kale
Summary: The study investigates the structural rearrangements of CENP-A nucleosomes resulting from antibody binding, showing that the antibodies can alter the dynamics of the nucleosomal core and indirectly affect the surrounding DNA. The binding of antibodies to the histone octamer surface is associated with conformational changes in CENP-A nucleosomes, indicating a more drastic impact compared to canonical nucleosomes. In addition, evidence suggests that the antibodies bind different octamer facades at varying affinities, revealing another level of complexity in DNA sequence regulation.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Catherine Naughton, Covadonga Huidobro, Claudia R. Catacchio, Adam Buckle, Graeme R. Grimes, Ryu-Suke Nozawa, Stefania Purgato, Mariano Rocchi, Nick Gilbert
Summary: This study reveals the special chromatin structure of centromeres, with centromere repositioning triggering transcriptional activation, epigenetic remodelling, and chromatin fiber decompaction. Analysis of a neocentromere suggests that transcription disrupts chromatin to provide a foundation for kinetochore formation, while compact pericentromeric heterochromatin generates mechanical rigidity.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Kai Walstein, Arsen Petrovic, Dongqing Pan, Birte Hagemeier, Dorothee Vogt, Ingrid R. Vetter, Andrea Musacchio
Summary: By reconstituting the human kinetochore component CENP-C, researchers have discovered a new structure and function, indicating that human kinetochores are formed by clustering multiple copies of a fundamental module, which may have important implications for transgenerational inheritance.
Article
Biochemistry & Molecular Biology
Marion E. Pesenti, Tobias Raisch, Duccio Conti, Kai Walstein, Ingrid Hoffmann, Dorothee Vogt, Daniel Prumbaum, Ingrid R. Vetter, Stefan Raunser, Andrea Musacchio
Summary: This study presents the structure of human CCAN and identifies some unique features, providing insights into the specific recognition mechanism of CENP-A nucleosome.
Review
Genetics & Heredity
Mariko Ariyoshi, Tatsuo Fukagawa
Summary: This article provides an update on the recent functional and structural studies of the kinetochore, a supramolecular complex that is essential for accurate chromosome segregation. It highlights the dynamic organization and key components of the inner kinetochore subcomplex, as well as its role in regulating temporal and spatial mechanisms of chromosome segregation.
TRENDS IN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Zhongyang Lin, Karen Wing Yee Yuen
Summary: In Caenorhabditis elegans, foreign DNA microinjection forms episomal extra chromosomal arrays or artificial chromosomes in embryos. These ACs undergo chromatinization and centromerization, with components like inner centromere, inner kinetochore, and spindle checkpoint factors assembling onto them. The DNA replication efficiency of ACs improves over cell cycles and is correlated with kinetochore bi-orientation and proper segregation of ACs, affected by proteins like condensin II subunits. Additionally, histone acetylation factors and chromatinization-related proteins play essential roles in the formation and competency of nascent ACs.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Stanislau Yatskevich, David Barford, Kyle W. Muir
Summary: Kinetochores are protein complexes on centromeric chromatin that facilitate chromosome segregation. Recent cryo-EM studies have revealed the structural conservation of CCAN, which plays a role in kinetochore assembly. Centromere recognition is primarily determined by engagement of duplex DNA near CENP-A nucleosomes through a DNA-binding CENP-LN channel. The enclosed DNA-binding chamber formed by other CCAN modules explains how kinetochores maintain their grip on centromeric DNA.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Benjamin Craske, Thibault Legal, Julie P. I. Welburn
Summary: In this study, we characterized the motility of human CENP-E in vitro and found that the full-length form exhibits longer run length and residency times on microtubules compared to motor truncations. We also discovered that the non-motor coiled-coil regions self-regulate the motor activity. These findings provide a useful tool to study the mechanistic basis of how human CENP-E drives chromosome congression and spindle organization.
Article
Chemistry, Medicinal
Youchao Deng, Sunbin Deng, Yi-Hsun Ho, Sarah M. Gardner, Zhi Huang, Ronen Marmorstein, Rong Huang
Summary: The study designed and prepared a series of highly potent NatD bisubstrate inhibitors, showing high specificity towards NatD and strong competitive characteristics, providing a rational path for future inhibitor development.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Cell Biology
Peiyu Xu, Sijie Huang, Brian E. Krumm, Youwen Zhuang, Chunyou Mao, Yumu Zhang, Yue Wang, Xi-Ping Huang, Yong-Feng Liu, Xinheng He, Huadong Li, Wanchao Yin, Yi Jiang, Yan Zhang, Bryan L. Roth, H. Eric Xu
Summary: The dopaminergic system and its receptors (D1R to D5R) have important roles in the central nervous system. This study presents cryo-EM structures of all five subtypes of human dopamine receptors complexed with G protein and the pan-agonist rotigotine. The structures provide insight into rotigotine recognition, ligand polypharmacology, receptor activation, unique receptor subtype features, and G protein coupling specificity. This work offers a comprehensive set of structural templates for the development of specific ligands to target dopaminergic system-related CNS diseases.
Article
Multidisciplinary Sciences
Yansheng Ye, Erin R. Tyndall, Van Bui, Zhenyuan Tang, Yan Shen, Xuejun Jiang, John M. Flanagan, Hong-Gang Wang, Fang Tian
Summary: The enzyme Atg3 is crucial for autophagosome formation, facilitating the connection of LC3 to PE lipids. The N-terminal conserved region of human Atg3 communicates information from the curvature-sensing domain to the active site, promoting spatial regulation of LC3-PE conjugation on target membranes.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Vishnu M. Nair, Amit Santhu Sabu, Ahmed Hussain, Delvin P. Kombarakkaran, R. Bhagya Lakshmi, Tapas K. Manna
Summary: This study reveals that the E3 ubiquitin ligase SCF-FBXW7 regulates the spindle assembly checkpoint (SAC) in human cells by mediating the degradation of BubR1. This mechanism controls the stability of BubR1 and its associated protein CENP-E at kinetochores. In addition, the study shows that the phosphorylation of BubR1 by Cdk1 plays a crucial role in FBXW7-mediated BubR1 ubiquitination.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Multidisciplinary Sciences
Ganesan Arunkumar, Songjoon Baek, David Sturgill, Minh Bui, Yamini Dalal
Summary: This study reveals that transcription of oncogenic lncRNAs derived from 8q24 alters chromatin structure, leading to the deposition of CENP-A-associated complexes at fragile sites in human cancer cells, generating new epigenetic memory.
Article
Cell Biology
Shengnan Zheng, Biyu Zheng, Zhenbang Liu, Xiaopeng Ma, Xing Liu, Xuebiao Yao, Wenfan Wei, Chuanhai Fu
Summary: This study identifies the key role of Cdc42 GTPase-activating protein Rga6 in regulating the localization of the septin complex and proposes a model where Rga6 regulates polarized cell growth by promoting targeted localization of the septin complex.
JOURNAL OF CELL SCIENCE
(2022)
Letter
Cell Biology
Wenwen Wang, Fengrui Yang, Jie Lin, Saravanakumar Muthusamy, Shihao Du, McKay Mullen, Fatima Garba, Wanjuan Wang, Xu Liu, Tao Li, Zhihong Yang, Xia Ding, Felix Aikhionbare, Xinjiao Gao, Zhikai Wang, Xing Liu, Xuebiao Yao
JOURNAL OF MOLECULAR CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sikai Liu, Xiao Yuan, Ping Gui, Ran Liu, Olanrewaju Durojaye, Donald L. Hill, Chuanhai Fu, Xuebiao Yao, Zhen Dou, Xing Liu
Summary: In mitosis, the interaction between Cyclin B2 and Mad2 guides accurate chromosome segregation through their localization at the kinetochores.
Article
Biochemistry & Molecular Biology
Yaqian Liu, Ruoxing Jin, Hui Lu, Kangjie Bian, Rui Wang, Lei Wang, Rui Gao, Jiahai Zhang, Jihui Wu, Xuebiao Yao, Xing Liu, Dan Liu, Xisheng Wang, Zhiyong Zhang, Ke Ruan
Summary: YEATS family proteins recognize acylated histones and regulate chromatin structure, gene transcription, and stress signaling. In this study, researchers identified inhibitors for the AF9 YEATS domain and designed new inhibitors based on complex structures and affinity assays. These inhibitors showed antiproliferation activities in AF9-sensitive cancer cells. This work provides a basis for further optimization of AF9 YEATS inhibitors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Chuan Huang, Yu Wang, Peng Chen, Qing-Hong Shan, Hao Wang, Lu-Feng Ding, Guo-Qiang Bi, Jiang-Ning Zhou
Summary: This study used a rabies-virus system to map the single-cell input onto corticotropin-releasing factor (CRF) neurons in the central amygdala (CeA). The inputs were found to be located in 44 nested subregions, with most of them being top-down convergent inputs from the cortex, especially in layer 4 of the somatosensory cortex, and relaying information from the thalamus. The bottom-up divergent inputs had a higher expression of glutamate decarboxylase. The study also revealed the en passant structures of single input neurons through in-situ reconstruction. These findings provide valuable insights into the circuit mechanisms of CeA-CRF neurons.
COMMUNICATIONS BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Zhaohuan Huang, Ling Liu, Jian Zhang, Kristie Conde, Jay Phansalkar, Zhongzhong Li, Lei Yao, Zihui Xu, Wei Wang, Jiangning Zhou, Guoqiang Bi, Feng Wu, Randy J. Seeley, Michael M. Scott, Cheng Zhan, Zhiping P. Pang, Ji Liu
Summary: This study identified a population of glucose-sensing GLP-1 receptor neurons in the dorsomedial hypothalamic nucleus, which can decrease blood glucose levels through communication with the pancreas. The mechanism by which this central GLP-1 signal controls glucose levels was also elucidated.
Article
Biochemistry & Molecular Biology
Ya Jiang, Ting Wang, Dandan Sheng, Chaoqiang Han, Tian Xu, Peng Zhang, Weiyi You, Weiwei Fan, Zhiyong Zhang, Tengchuan Jin, Xiaotao Duan, Xiao Yuan, Xing Liu, Kaiguang Zhang, Ke Ruan, Jue Shi, Jing Guo, Aoxing Cheng, Zhenye Yang
Summary: This study reveals a new protumor function of Aurora A by phosphorylating PKM2 during the S phase of the cell cycle to promote glycolysis and tumor growth. The spatial and temporal regulation of the specific kinase and PKM2 interaction is context dependent, showing intricate interconnectivity between cell cycle and glycolytic regulators.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Cell Biology
Divine Mensah Sedzro, Xiao Yuan, McKay Mullen, Umer Ejaz, Tongtong Yang, Xu Liu, Xiaoyu Song, Yun-Chi Tang, Weijun Pan, Peng Zou, Xinjiao Gao, Dongmei Wang, Zhikai Wang, Zhen Dou, Xing Liu, Xuebiao Yao
Summary: The study reveals that CENP-R collaborates with CENP-OPQU to regulate the stability of kinetochore-microtubule attachment and ensure accurate chromosome segregation during mitosis. Phosphorylation of CENP-R affects its localization to the kinetochore, possibly by disrupting its binding with CENP-U.
JOURNAL OF MOLECULAR CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Yun-Tao Liu, Heng Zhang, Hui Wang, Chang-Lu Tao, Guo-Qiang Bi, Z. Hong Zhou
Summary: IsoNet is a neural network that addresses the issue of anisotropic resolution in cryogenic electron tomography by learning and recovering feature representations of similar structures in the tomogram. Its application greatly improves the interpretability and visualization of cellular structures.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
Qiao-Qiong Liu, Yu-Xiao Cheng, Qi Jing, Ke-Ming Zhang, Lu-Feng Ding, Xiao-Wei Fan, Chun-Hui Jia, Fang Xu, Guo-Qiang Bi, Pak-Ming Lau
Summary: This study employed a dual-viral injection strategy to label cortical pyramidal neurons targeting the pedunculopontine nucleus (PPN) in mice. By using a high-speed volumetric imaging technique, the researchers visualized the brain-wide axonal projections of these neurons from various cortical areas and identified unique collateralization patterns to different subcortical areas. The findings provide potential anatomical mechanisms for the coordination between the PPN and other subcortical areas in performing different physiological functions.
Article
Cell Biology
Yanze Jian, Lingyun Nie, Sikai Liu, Yueyue Jiang, Zhen Dou, Xing Liu, Xuebiao Yao, Chuanhai Fu
Summary: The outer kinetochore acts as a platform for SAC initiation and mediating kinetochore-microtubule attachments. The inner kinetochore subcomplex CENP-S-CENP-X's involvement in regulating the SAC and kinetochore-microtubule attachments is not well characterized.
JOURNAL OF CELL SCIENCE
(2023)
Article
Cell Biology
Xiaoyu Song, Fengrui Yang, Tongtong Yang, Yong Wang, Mingrui Ding, Linge Li, Panpan Xu, Shuaiyu Liu, Ming Dai, Changbiao Chi, Shengqi Xiang, Chao Xu, Dong Li, Zhikai Wang, Lin Li, Donald L. Hill, Chuanhai Fu, Kai Yuan, Pilong Li, Jianye Zang, Zhonghuai Hou, Kai Jiang, Yunyu Shi, Xing Liu, Xuebiao Yao
Summary: EB1 proteins form molecular condensates through liquid-liquid phase separation (LLPS) to constitute the microtubule plus-end machinery, which is crucial for cellular dynamics and organelle movements.
NATURE CELL BIOLOGY
(2023)
Article
Neurosciences
Xiao-Wei Li, Yi Ren, Dong-Qing Shi, Lei Qi, Fang Xu, Yanyang Xiao, Pak-Ming Lau, Guo-Qiang Bi
Summary: Acetylcholine (ACh) affects neural circuit dynamics by inhibiting excitatory synaptic transmission and enhancing neuronal excitability through muscarinic signaling pathways. It suppresses evoked reverberation at low to moderate doses, while high doses result in longer duration of reverberation and increased spontaneous activity. These effects are mediated by muscarinic, but not nicotinic receptors, and can be simulated through changes in excitatory postsynaptic currents (EPSCs) and the excitability of single cells.
NEUROSCIENCE BULLETIN
(2023)
Letter
Neurosciences
Dong-Qing Shi, Fang Xu, Guo-Qiang Bi, Pak-Ming Lau
NEUROSCIENCE BULLETIN
(2023)
Article
Neurosciences
Ke-Ming Zhang, Yan Shen, Chun-Hui Jia, Hao Wang, Guo-Qiang Bi, Pak-Ming Lau
Summary: Cooperation is a vital social behavior for survival, and a new paradigm was developed to train and test cooperative behavior in mice. The study found extensive social contact and waiting behavior, which were positively correlated with the success of cooperation. Using c-Fos immunostaining and high-speed volumetric imaging, the researchers identified increased neuronal activity in cortical areas during cooperation, providing insights into the underlying neural circuitry mechanisms.
