Article
Cell Biology
Anna M. Dowbaj, Robert P. Jenkins, Daniel Williamson, John M. Heddleston, Alessandro Ciccarelli, Todd Fallesen, Klaus M. Hahn, Reuben D. O'Dea, John R. King, Marco Montagner, Erik Sahai
Summary: The shuttle of transcription factors and transcriptional regulators is crucial for the regulation of biological processes. A new method involving optogenetic release of YAP1 and TAZ from sequestration demonstrates the correlation between their rates of entry and exit. Phosphorylation influences YAP1's rate of nuclear export, indicating a complex regulatory mechanism for protein dynamics.
JOURNAL OF CELL SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Shiho Hisaoka, Jin Osawa, Riku Kobashi, Atsuhiko Ishida, Isamu Kameshita, Noriyuki Sueyoshi
Summary: Research has shown that BMP2-inducible kinase (BMP2K) forms liquid-liquid phase separated droplets in the cytoplasm, regulated by a glutamine-rich area and hyperosmolarity. The cytoplasmic localization of BMP2K is managed through the inhibition of nuclear localization signal (NLS) function via phosphorylation of Ser-1010 and the antagonism of the NLS by a newly discovered cytoplasmic localization region. These findings provide a biochemical foundation for the advancement of BMP2K-related cell biology, structural biology, and pathophysiology.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Laura Martinez-Arenas, Jose R. Bayascas
Summary: PDK1 is a constitutively active master kinase that can phosphorylate and activate multiple enzymes of the AGC family. In this issue of Science Signaling, Sacerdoti et al. uncover the mechanisms by which allosteric communication directs the selectivity of PDK1 towards specific subsets of substrates.
Article
Plant Sciences
Joseph Yayen, Ching Chan, Ching-Mei Sun, Su-Fen Chiang, Tzyy-Jen Chiou
Summary: The number of genes encoding receptor-like kinases (RLKs) has expanded in land plants, resulting in diverse domain architectures. This study focused on RLCK XI, a subfamily of receptor-like cytoplasmic kinases in plants. The researchers discovered a long kinase insert domain (KID) between subdomains VII and VIII in RLCK XI, with an average length of 280 amino acids. This unique KID architecture was found in several hornwort and liverwort species. The KID showed a high propensity for being disordered and contained repetitive nuclear localization signals, suggesting a dual localization of RLCK XI from the plasma membrane to the nucleus.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Multidisciplinary Sciences
Minako Hirano, Masahisa Tomita, Chikako Takahashi, Nobuyuki Kawashima, Toru Ide
Summary: By optimizing gold probes and developing an automated measurement system, this study successfully improved the efficiency of ion channel current measurements and membrane stability. This advancement allows for automatic measurement of channel currents and analysis of the effects of blockers on channel activity.
SCIENTIFIC REPORTS
(2021)
Review
Cell Biology
Szabolcs Sipeki, Kitti Koprivanacz, Tamas Takacs, Anita Kurilla, Loretta Laszlo, Virag Vas, Laszlo Buday
Summary: Signal transduction is essential for cells to perceive and respond to information, with subcellular hubs formed via protein interactions playing a central role. The SH2 and SH3 domains serve as prototypes for interaction domains that recognize proteins, lipids, nucleic acids, and small molecules. The lipid-binding properties of SH2 and SH3 domains are also important for modulating complex assembly.
Article
Multidisciplinary Sciences
Nuria Gallisa-Sune, Paula Sanchez-Fernandez-de-Landa, Fabian Zimmermann, Marina Serna, Laura Regue, Joel Paz, Oscar Llorca, Jens Luders, Joan Roig
Summary: This study demonstrates that the adaptor protein BICD2 is activated through phosphorylation, which promotes the formation of the dynein motor complex and regulates its localization and activity within cells. This finding is crucial for understanding the functional importance of dynein in both dividing and non-dividing cells.
NATURE COMMUNICATIONS
(2023)
Article
Genetics & Heredity
Julia Madsen-Osterbye, Mohamed Abdelhalim, Sarah Hazell Pickering, Philippe Collas
Summary: This study reveals that the nuclear lamina provides a repressive chromatin environment, and most genes in lamina-associated domains (LADs) are inactive. However, over ten percent of the genes in LADs are active. The study shows that the inferred enhancers of active genes in LADs can interact with other enhancers inside and outside LADs, and the distance between differentially expressed genes in LADs and distant enhancers changes during adipogenic differentiation. The involvement of lamin A/C in repressing genes in the border of an in-LAD active region within a topological domain is also shown.
Article
Multidisciplinary Sciences
Kyle I. P. Le Huray, He Wang, Frank Sobott, Antreas C. Kalli
Summary: This study systematically simulated the interactions between 100 mammalian PH domains and PIP-containing membranes. The observed PIP interaction hotspots recapitulate crystallographic binding sites and provide insights into the mechanisms of PH domain/membrane association. The study offers a comprehensive view of the binding of PH domains to membranes.
Article
Pharmacology & Pharmacy
Yasi Ding, Weibin Tang, Fei Pei, Lixia Fu, Pei Ma, Jinye Bai, Mingbao Lin, Yunbao Liu, Qi Hou
Summary: Bru-34 significantly attenuated allergic airway inflammation by modulating the expression of inflammatory proteins and reducing the Syk-cPLA2-NF-κB signaling pathway.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Cell Biology
Jae-Sook Park, Yiying Hu, Nancy M. Hollingsworth, Gabriel Miltenberger-Miltenyi, Aaron M. Neiman
Summary: VPS13 family proteins mediate lipid transfer between organelle membranes and are associated with various genetic disorders. This study reveals the crucial role of the C-terminal pleckstrin homology (PH) domain of VPS13A in the formation of a complex with XK scramblase and their co-localization within cells. Mutations in this region disrupt the complex formation and co-localization of both proteins.
JOURNAL OF CELL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Ismael Y. Karkache, Jeyaram R. Damodaran, David H. H. Molstad, Kim C. Mansky, Elizabeth W. Bradley
Summary: Phlpp1 deficiency within myeloid lineage cells enhances bone mass by limiting bone resorption, repressing osteoclastogenesis, and controlling responses to M-CSF.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Microbiology
Hye Won Lee, Yongwook Choi, Ah Ram Lee, Cheol-Hee Yoon, Kyun-Hwan Kim, Byeong-Sun Choi, Yong Kwang Park
Summary: This study found that HGF-induced ACK1 inhibits HBV replication at the transcriptional level through activation of the MAPK-HNF signaling pathway, leading to suppression of viral gene expression and transcription, as well as decreased viral enhancer activity.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Polymer Science
Eden Mariam Jacob, Ankita Borah, Sindhu C. Pillai, D. Sakthi Kumar
Summary: pH-sensitive nanoscale particles designed in this study could release drug specifically in colonic pH environment, targeting inflamed tissues in inflammatory bowel disease and reducing inflammation. In vitro experiments demonstrated the biocompatibility of these nanoparticles and their ability to inhibit inflammatory responses.
Article
Biochemical Research Methods
Toshihiko Sugiki, Young-Ho Lee, Nesreen Alsanousi, Kaito Murata, Izuru Kawamura, Toshimichi Fujiwara, Kentaro Hanada, Chojiro Kojima
Summary: In this study, we demonstrated that a specific interaction between the pleckstrin homology (PH) domain of ceramide transport protein (CERT) and phosphatidylinositol 4-monophosphate (PI4P) can be detected using structural and thermodynamic analyses. This interaction can be distinguished from nonspecific interactions with the bulk surface of the lipid nanodisc. Our NMR-ITC hybrid strategy provides detailed characterization of protein-lipid membrane interactions.
ANALYTICAL BIOCHEMISTRY
(2022)
Article
Oncology
Feng-Min Liu, Yu-Fei Gao, Yanyan Kong, Yihui Guan, Jinsen Zhang, Shuai-Hong Li, Dan Ye, Wenyu Wen, Chuantao Zuo, Wei Hua
Summary: The SUVmax on PET can predict IDH1 mutation with high sensitivity and specificity, supported by reduced glucose consumption in IDH1 mutant gliomas, as evidenced by changes in glucose quantity and metabolic enzyme expression levels.
Article
Cell Biology
Qixu Cai, Menglong Zeng, Xiandeng Wu, Haowei Wu, Yumeng Zhan, Ruijun Tian, Mingjie Zhang
Summary: CaMKIIα plays a crucial role in synapses by interacting with Shank3 and GluN2B, regulating synaptic plasticity through the modulation of Ca2+ concentration and phosphatases. The shuttling of CaMKIIα between specific PSD subcompartments and PSD condensates controlled by protein phosphatases contributes to PSD assembly enlargement and structural long-term potentiation.
Article
Chemistry, Medicinal
Jie Zang, Fei Ye, Sara M. o. Solbak, Lars J. Hoj, Mingjie Zhang, Anders Bach
Summary: The study focused on the druggability of the PSD-95 PDZ1-2 domain, using fragment screening to identify four promising fragments that could serve as starting points for small-molecule PDZ domain inhibitors optimization. The results demonstrate the successful application of fragment screening to PDZ1-2 of PSD-95, unveiling novel fragments with potential for drug development.
Article
Neurosciences
Yasunori Hayashi, Lenzie K. Ford, Luana Fioriti, Leeanne McGurk, Mingjie Zhang
Summary: LLPS is a new mechanism for cellular compartmentalization, recently gaining attention in neurobiology. It typically occurs between macromolecules with multivalent interactions, aiding in the formation of membraneless organelles.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Jin Ye, Guichang Zou, Ruichi Zhu, Chao Kong, Chenjian Miao, Mingjie Zhang, Jianchao Li, Wei Xiong, Chao Wang
Summary: GABARAP and GABARAPL1 stabilize GABA(A) receptors by directly binding to the γ 2 subunit, promoting receptor trafficking pathways, and modulating receptor localization at synapses.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Physical
Hasan Cinar, Rosario Oliva, Haowei Wu, Mingjie Zhang, Hue Sun Chan, Roland Winter
Summary: The study reveals the high pressure sensitivity of the SynGAP/PSD-95 system and suggests that deep-sea organisms counteract this sensitivity to avoid neurological impairment. The findings offer insights into the neurological effects of hydrostatic pressure and potential strategies to alleviate pressure-induced neurological disorders.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Biology
Xuan Pei, Kai-Yue Li, Yuan Shen, Jin-Tao Li, Ming-Zhu Lei, Cai-Yun Fang, Hao-Jie Lu, Hui-Juan Yang, Wenyu Wen, Miao Yin, Jia Qu, Qun-Ying Lei
Summary: In epithelial ovarian cancer, palmitoylation of MDH2 mediated by ZDHHC18 enhances MDH2 activity, promoting the growth and malignancy of ovarian cancer. Targeting ZDHHC18-mediated MDH2 palmitoylation may be a potential therapeutic approach for EOC.
SCIENCE CHINA-LIFE SCIENCES
(2022)
Article
Cell Biology
Zhe Feng, Suho Lee, Bowen Jia, Tao Jian, Eunjoon Kim, Mingjie Zhang
Summary: The scaffold protein IRSp53 plays an important role in synapse development and synaptic plasticity. This study reveals that specific interactions between IRSp53 and its binding partners PSD-95 or Shank3 drive phase separation of complexes and promote synaptic enrichment of IRSp53 in mouse cortical neurons. The study also highlights the role of IRSp53 in actin filament formation and synaptic maturation. These findings provide mechanistic insights into the physiological roles of IRSp53 in synapse formation and function.
JOURNAL OF CELL BIOLOGY
(2022)
Letter
Cell Biology
Yanan Wu, Min Zhang, Yizheng Yang, Xuyang Ding, Ping Yang, Kai Huang, Xinlin Hu, Mingjie Zhang, Xiaotian Liu, Hongjun Yu
Article
Multidisciplinary Sciences
Amit Kumar Gaurav, Marjia Afrin, Xian Yang, Arpita Saha, S. K. Abdus Sayeed, Xuehua Pan, Zeyang Ji, Kam-Bo Wong, Mingjie Zhang, Yanxiang Zhao, Bibo Li
Summary: Trypanosoma brucei is a protozoan parasite that causes human African trypanosomiasis. TbRAP1, a telomere protein, has been shown to silence VSG genes by binding to dsDNA. However, the mechanism by which TbRAP1 allows the expression of a single active VSG gene was unknown. In this study, the researchers unexpectedly discovered an RNA Recognition Motif (RRM) in TbRAP1, which is unprecedented for RAP1 homologs. They found that TbRAP1 RRM, assisted by a specific patch, can recognize and bind to the 3'UTR sequences of VSG genes. Mutating the conserved residues in RRM abolished RNA binding activity, significantly decreased the level of active VSG RNA, and derepressed silent VSG genes. Their findings suggest a monoallelic expression mechanism for VSG genes, in which the abundant RNA of the active VSG gene antagonizes TbRAP1's silencing effect.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Qixu Cai, Xiumin Chen, Shihan Zhu, Roger A. Nicoll, Mingjie Zhang
Summary: Calcium calmodulin-dependent kinase II (CaMKII) is crucial for synaptic transmission and plasticity. The length of the unstructured linker between the kinase domain and the oligomerizing hub plays a crucial role in determining the ability of CaMKII to rescue defects in synaptic transmission and long-term potentiation. The phase separation capacity of CaMKII with GluN2B is critical for its cellular functions in the brain.
Article
Biology
Zeyu Shen, Bowen Jia, Yang Xu, Jonas Wessen, Tanmoy Pal, Hue Sun Chan, Shengwang Du, Mingjie Zhang, Rohit Pappu
Summary: Formation of membraneless organelles or biological condensates via phase separation expands the cellular organelle repertoire. In this study, an adaptive single-molecule imaging method was developed to track individual molecules in various biological condensates. The method enables measurements of concentrations, motion behavior, and molecular exchanges between condensed and dilute phases. The findings offer insights into the molecular mechanisms underlying the assembly and dynamics of biological condensates.
Article
Biology
Xudong Chen, Bowen Jia, Shihan Zhu, Mingjie Zhang
Summary: The volume and electric strength of an excitatory synapse are correlated with the area of its postsynaptic density (PSD). The molecular mechanism underlying the communication between the PSD assembly and spine actin cytoskeleton is poorly understood. This study discovers that PSD condensates can promote actin polymerization and bundling, and the Homer scaffold protein and a positively charged actin-binding surface of the Homer EVH1 domain are essential for this process. The communication between PSD and spine cytoskeleton may be modulated by targeting the phase separation of the PSD condensates.
Article
Multidisciplinary Sciences
Meng Zhang, Aili Cao, Lin Lin, Ying Chen, Yuan Shang, Chao Wang, Mingjie Zhang, Jinwei Zhu
Summary: The truncated guanylate kinase (GK) domain of MAGI2 interacts with its adjacent PDZ0 domain to form a supramodule capable of recognizing phosphoproteins. Identification of a phosphorylation-dependent binding motif for PDZ0-GK leads to the discovery of previously unknown binding partners. The structure and function of the MAGI2-target complex is explored using an inhibitory peptide derived from the consensus motif, revealing the action mechanism of cryptic MAGI GKs and broadening our understanding of target recognition rules of phosphoprotein binding modules.
Article
Multidisciplinary Sciences
Jingyu Li, Kang Zhu, Aihong Gu, Yiqing Zhang, Shijing Huang, Ronggui Hu, Weiguo Hu, Qun-Ying Lei, Wenyu Wen
Summary: Lipid homeostasis is crucial for cellular functions and its dysregulation is associated with human diseases. This study demonstrates that Spartin promotes the formation of Itch condensates independently of lipid droplets, activates Itch through self-oligomerization, and accelerates the generation of polyubiquitin chains through liquid-liquid phase separation, forming a positive feedback loop. These findings provide important insights into lipid metabolism and autophagic degradation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Ankita Chadda, Alexander G. Kozlov, Binh Nguyen, Timothy M. Lohman, Eric A. Galburt
Summary: In this study, it was found that the DNA damage response in Mycobacterium tuberculosis differs from well-studied model bacteria. The DNA repair helicase UvrD1 in Mtb is activated through a redox-dependent process and is closely associated with the homo-dimeric Ku protein. Additionally, Ku protein is shown to stimulate the helicase activity of UvrD1.
JOURNAL OF MOLECULAR BIOLOGY
(2024)
