Article
Cell Biology
M. J. Grubisha, R. A. DeGiosio, Z. P. Wills, R. A. Sweet
Summary: This review summarizes emerging data on the roles of Rac1 and RhoA as cytoskeletal regulators and highlights their importance in spatiotemporal regulation. Recent studies have shown that precise spatiotemporal regulation of Rac1 and RhoA is crucial for cell structure, function, and migration.
CELLULAR SIGNALLING
(2022)
Article
Immunology
Kirsti Hornigold, Martin J. Baker, Polly A. Machin, Stephen A. Chetwynd, Anna-Karin Johnsson, Chiara Pantarelli, Priota Islam, Melanie Stammers, Laraine Crossland, David Oxley, Hanneke Okkenhaug, Simon Walker, Rachael Walker, Anne Segonds-Pichon, Yoshinori Fukui, Angeliki Malliri, Heidi C. E. Welch
Summary: Tiam1 is a novel regulator of Rac-dependent neutrophil responses, controlling adhesion, migration, reactive oxygen species generation, degranulation, NETs release, and bacterial killing. It functions differently from other Rac-GEFs by restricting neutrophil adhesion and beta 2 integrin activity, and by promoting the expression of regulators of small GTPases and cytoskeletal dynamics.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Paola Matarrese, Rosa Vona, Barbara Ascione, Marco G. Paggi, Anna Maria Mileo
Summary: The study demonstrates that the interaction between HPV16 E7 and gelsolin promotes cytoskeleton rearrangement, leading to epithelial-mesenchymal transition and activating the HIPPO signaling pathway. This may play a role in the acquisition of a more aggressive phenotype in HPV16-transformed cells, providing potential therapeutic targets for HPV-related cancers.
Review
Cell Biology
Emily J. Koubek, Lorraine C. Santy
Summary: Dock1, also known as Dock180, is the first member identified in the Dock family of GTPase Exchange Factors. It activates Rac to stimulate actin polymerization and is involved in various cellular processes. Inappropriate activity of Dock180 has been implicated in cancer invasion, metastasis, and bacterial pathogen uptake.
Article
Biology
Judith Pineau, Lea Pinon, Olivier Mesdjian, Jacques Fattaccioli, Ana-Maria Lennon Dumenil, Paolo Pierobon
Summary: Immune synapse formation is a crucial step for lymphocyte activation. The roles of actin and microtubule cytoskeletons in synapse formation are well-known, but the coordination of different events involved in synapse formation by actin-microtubule interactions remains unclear. By using a microfluidic pairing device, the study provides unprecedented resolution in understanding the dynamics of synapse formation in B cells. The results reveal the dominance of actin and microtubule dynamics in local and global events, respectively, and also highlight the unexpected role of microtubules and the GEF-H1-RhoA axis in controlling F-actin polymerization for the formation and maintenance of a functional immune synapse.
Article
Oncology
Carmela Gomez, Rosula Garcia-Navas, Fernando C. Baltanas, Rocio Fuentes-Mateos, Alberto Fernandez-Medarde, Nuria Calzada, Eugenio Santos
Summary: This study demonstrates the protective role of SOS1 deficiency in the development of CML and identifies it as a novel therapeutic target.
Article
Urology & Nephrology
Roberto Boi, Lovisa Bergwall, Kerstin Ebefors, Martin O. Bergo, Jenny Nystrom, Lisa Buvall
Summary: Loss of geranylgeranylation in podocytes leads to progressive albuminuria and foot process effacement in podocyte-specific GGTase-I knockout mice. Absence of geranylgeranylation results in altered activity of downstream substrates Rac1, RhoA, Cdc42, and Rap1, leading to changes in β1-integrins and actin cytoskeleton structure in cultured podocytes.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Chemistry, Multidisciplinary
Andrzej Kubiak, Matteo Chighizola, Carsten Schulte, Natalia Bryniarska, Julita Wesolowska, Maciej Pudelek, Malgorzata Lasota, Damian Ryszawy, Agnieszka Basta-Kaim, Piotr Laidler, Alessandro Podesta, Malgorzata Lekka
Summary: The study demonstrates that anticancer microtubule targeting drugs can induce cell stiffening by directly perturbing the structural organization of microtubules. While changes in cellular rigidity are typically attributed to remodeling of actin filaments in the cytoskeleton, it is also shown that cell stiffening can be driven by crosstalk between actin filaments and microtubules in MTD-treated cells. These findings improve the interpretation of biomechanical data obtained for living cells in studies of various physiological and pathological processes.
Article
Chemistry, Physical
Shailaja Seetharaman, Benoit Vianay, Vanessa Roca, Aaron J. Farrugia, Chiara De Pascalis, Batiste Boeda, Florent Dingli, Damarys Loew, Stephane Vassilopoulos, Alexander Bershadsky, Manuel Thery, Sandrine Etienne-Manneville
Summary: Mechanotransduction is a process where cells sense mechanical properties of their environment, with integrin-mediated focal adhesions being crucial sites. The crosstalk between microtubules and actin in mechanotransduction affects cell adhesion and migration. Substrate-rigidity-dependent microtubule acetylation controls YAP translocation, focal adhesion distribution, actomyosin contractility, and cell migration.
Article
Biochemistry & Molecular Biology
Maxime Bonnet, Fiona Roche, Christine Fagotto-Kaufmann, Gabriella Gazdagh, Iona Truong, Franck Comunale, Sonia Barbosa, Marion Bonhomme, Nicolas Nafati, David Hunt, Monserrat Pons Rodriguez, Ayeshah Chaudhry, Deborah Shears, Marcos Madruga, Fleur Vansenne, Aurore Curie, Andrey V. V. Kajava, Diana Baralle, Coralie Fassier, Anne Debant, Susanne Schmidt
Summary: Mutations in the TRIO gene are associated with neurodevelopmental disorders by hyperactivating the RAC1 GTPase. By combining clinical, molecular, cellular, and in vivo data, we provide new evidence for the pathogenicity of TRIO gene mutations and propose a novel mechanism for their impact on neuronal development.
MOLECULAR PSYCHIATRY
(2023)
Article
Cell Biology
Batel Shalom, Marganit Farago, Yaser Salaymeh, Shulamit Sebban, Eli Pikarsky, Shulamit Katzav
Summary: Vav1 is normally expressed in the hematopoietic system and its mutations and overexpression are associated with malignancies. This study shows that Vav1 expression in epithelial tissues can lead to the development of B-cell lymphomas. The cross-talk between epithelial cells secreting CSF-1 and lymphocytes expressing CSF-1R may contribute to the generation of these lymphomas.
Article
Biochemistry & Molecular Biology
Mutsuko Kukimoto-Niino, Kentaro Ihara, Kazutaka Murayama, Mikako Shirouzu
Summary: The DOCK family of guanine nucleotide exchange factors regulates cytoskeletal dynamics by activating Rac and/or Cdc42 GTPases, playing important roles in development and the immune system. Recent structural studies have improved understanding of DOCK GEF activity and GTPase recognition, focusing on how Rac and Cdc42 are specifically recognized.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Nikolaus Dietz, Markus Huber, Isabel Sorg, Arnaud Goepfert, Alexander Harms, Tilman Schirmer, Christoph Dehio
Summary: The bacterial effector protein Bep1 selectively targets members of the Rac subfamily in the Rho family of small GTPases based on electrostatic interactions, providing a highly selective tool for functional analysis of these GTPases. This study establishes a structural understanding of target selectivity towards Rac-subfamily GTPases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Genetics & Heredity
Yuli T. Magalhaes, Jessica O. Farias, Luiz E. Silva, Fabio L. Forti
Summary: The classical small Rho GTPase protein family plays crucial roles in regulating cell functions, including maintaining genomic stability and participating in DNA damage response. Studies have shown that direct modulation of Rho GTPase activity, its downstream effectors, and actin cytoskeleton regulation can impact cellular events.
Article
Cell Biology
Emily S. Wilson, Karen Litwa
Summary: Hyaluronan synthase-2 is crucial in the development of neural circuits, with increased hyaluronan production reducing excitatory synapses, promoting inhibitory synaptogenesis, and suppressing action potential formation. The hyaluronan receptor, CD44, plays a role in hyaluronan retention and regulation of excitatory synaptogenesis through RhoGTPase signaling.
Article
Cell Biology
Ke Mi, Lizhong Zeng, Yang Chen, Jingya Ning, Siyuan Zhang, Peilin Zhao, Shuanying Yang
Summary: In this study, the researchers explored the role of DHX38 in NSCLC and its underlying molecular mechanism. They found that DHX38 was overexpressed in NSCLC and patients with high DHX38 expression had poor prognosis. DHX38 promoted cell proliferation, migration, and invasion in NSCLC and activated the MAPK pathway. The researchers also identified G3BP1 as a target protein that interacted with DHX38 and showed that DHX38 regulated the expression of G3BP1. Silencing G3BP1 reversed the effects of DHX38 overexpression on tumor cell proliferation, migration, and invasion and inhibited the MAPK pathway activation.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Tiina A. Jokela, Mark A. Dane, Rebecca L. Smith, Kaylyn L. Devlin, Sundus Shalabi, Jennifer C. Lopez, Masaru Miyano, Martha R. Stampfer, James E. Korkola, Joe W. Gray, Laura M. Heiser, Mark A. Labarge
Summary: Microenvironment signals have a significant impact on cell fate and tissue homeostasis. Understanding how different microenvironment factors regulate cellular phenotype has been challenging. In this study, a high-throughput microenvironment microarray was used to identify factors that support the proliferation and maintenance of primary human mammary luminal epithelial cells. Multiple factors that modulate luminal cell number were identified and their effects were confirmed using RNA sequencing and cell-based functional studies. Hepatocyte growth factor (HGF) was found to be robust to individual variation and played a role in expanding luminal cells. Our approach demonstrates the power of high-dimensional cell-based approaches in dissecting microenvironmental signals.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Chao He, Yongfeng Ding, Yan Yang, Gang Che, Fei Teng, Haohao Wang, Jing Zhang, Donghui Zhou, Yanyan Chen, Zhan Zhou, Haiyong Wang, Lisong Teng
Summary: This study categorized gastric cancer patients into three stemness subtypes, each demonstrating distinct prognoses, components of tumor microenvironment (TME) infiltration, and varying sensitivity or resistance to treatment. A stemness risk model was constructed to predict treatment response and prognosis.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Haile Zhao, Lijuan Feng, Rui Cheng, Man Wu, Xiaozhou Bai, Lifei Fan, Yaping Liu
Summary: miR-29c-3p is overexpressed in benign and malignant ovarian carcinoma and is associated with poor prognosis. Its overexpression modulates tumorigenesis in ovarian cancer cells, including epithelial-mesenchymal transition, proliferation, migration, and invasion, through the regulation of DNMT3A, TET1, and HBP1. miR-29c-3p may serve as a potential biomarker for clinical diagnosis or co-diagnosis of ovarian carcinoma.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Haiyan Zhao, Fangfang Bi, Mengyuan Li, Yuhan Diao, Chen Zhang
Summary: This study confirmed the tumor suppressor effect of RNF180 on ovarian cancer, elucidated the mechanism of the molecule network related to RNF180 and IPO4 in ovarian cancer, and identified a new therapeutic target for ovarian cancer.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Chu Chen, Guanhua Xu, Jiajia Chen, Chunshuai Wu, Jinlong Zhang, Jiawei Jiang, Hongxiang Hong, Zhiming Cui
Summary: This study investigated the role of transcription factor FoxO1 in facet joint osteoarthritis (FJOA) and found that FoxO1 deletion led to severe osteoarthritic changes. Transcriptome sequencing and bioinformatics analysis identified differentially expressed genes (DEGs) and potential key contributors to FJOA. Additionally, over-expression of certain genes and inhibition of others were shown to counteract the impairments caused by FoxO1 deletion in chondrocyte migration and extracellular matrix synthesis. These findings help unravel the molecular mechanisms underlying FJOA and open up promising therapeutic avenues for its treatment.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Wen Deng, Ru Chen, Situ Xiong, Jianqiang Nie, Hailang Yang, Ming Jiang, Bing Hu, Xiaoqiang Liu, Bin Fu
Summary: This study demonstrates that circFSCN1 is upregulated in bladder cancer and associated with cancer-specific survival. CircFSCN1 promotes tumor progression and epithelial-mesenchymal transition in bladder cancer through enhancing MDM2-mediated silencing of p53 by sponging miR-145-5p.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Jun Wu, Weibin Hu, Wenhui Yang, Yihao Long, Kaizhao Chen, Fugui Li, Xiaodong Ma, Xun Li
Summary: Cholesterol biosynthesis and metabolism play critical roles in tumor development and microenvironmental conditions. Squalene Epoxidase (SQLE), the second rate-limiting enzyme in cholesterol synthesis, is found to be uniquely expressed in various cancers, and its expression level is closely associated with tumor mutation burden and microsatellite instability. SQLE expression is negatively correlated with immune cell infiltration. Inhibition of SQLE alters the immune response in the tumor microenvironment. Furthermore, protein metabolism and translation are identified as main binding factors with SQLE.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Zhihong Zhang, Mingyue Li, Yi Tai, Yue Xing, Hongxiang Zuo, Xuejun Jin, Juan Ma
Summary: ZNF70 plays an important role in colitis-associated colorectal cancer (CAC) by regulating macrophages IL-1 beta secretion to promote HCT116 proliferation. It may serve as a promising target for treating CAC.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Zenghong Wu, Gangping Li, Weijun Wang, Kun Zhang, Mengke Fan, Yu Jin, Rong Lin
Summary: This study comprehensively explored the role of immune checkpoints and tumor microenvironment in gastric cancer patients based on genomic data. It constructed an ICIs signature and ICI score to evaluate patient prognosis and heterogeneity.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Yantong Wan, Jieshu Zhou, Panpan Zhang, Xuemei Lin, Hao Li
Summary: This study found that Rac1 plays a role in astrocyte activation and attenuates chronic inflammatory pain by blocking the phosphorylation of NLRP3 inflammasome and NF-kappa B.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Zhen Wang, Diankun She, Lei Liu, Xianming Hua, Hao Zhu, Lingfeng Yu, Han Wang, Yan Zhu, Gentao Fan, Yicun Wang, Meng Xu, Guangxin Zhou
Summary: Circular RNAs (circRNAs) are non-coding RNAs that play a role in the regulation of various cancers, including osteosarcoma (OS). This study identified circSATB2 as a highly expressed circRNA in OS tissues and cell lines, and demonstrated its involvement in promoting OS proliferation and migration. Mechanistically, circSATB2 was found to regulate the progression of OS by sponging miR-661 and FUS to regulate ZNFX1 mRNA. These findings suggest that circSATB2 could serve as a prognostic marker and therapeutic target for osteosarcoma.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Kenichi Ogata, Masafumi Moriyama, Tatsuya Kawado, Hiroki Yoshioka, Aiko Yano, Mayu Matsumura-Kawashima, Seiji Nakamura, Shintaro Kawano
Summary: This study found that extracellular vesicles released by induced pluripotent stem cells can reduce inflammatory cell infiltration, increase saliva volume, and decrease the production of antibodies associated with Sjogren's syndrome in a mouse model. The let-7 family in these vesicles may suppress the expression of TLR4 and NF-kappa B, which leads to the inhibition of pro-inflammatory cytokine production through the MAPK pathway.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Mikayla R. Erdelsky, Sarah A. Groves, Charmi Shah, Samantha B. Delios, M. Bibiana Umana, Donald H. Maurice
Summary: Recent evidence suggests that cAMP signaling within the primary cilium plays a crucial role in promoting adipogenic differentiation of 3T3-L1 preadipocytes. In this study, the researchers identified the specific cAMP phosphodiesterases expressed by these cells and found that inhibition of PDE4 promotes FFAR4-mediated adipogenesis. This work could potentially lead to the discovery of more targeted therapeutic approaches for controlling adipogenesis and differentiation of other stem cells.
CELLULAR SIGNALLING
(2024)
Article
Cell Biology
Chun-Hui Liu, Jun-Jie Zhang, Qian-Jin Zhang, Yang Dong, Zhen-Duo Shi, Si-Hao Hong, Hou-Guang He, Wei Wu, Cong-Hui Han, Lin Hao
Summary: Bladder cancer, the most common malignant tumor in the urinary system, is associated with significantly up-regulated expression of P3H4, which is regulated by METTL3 and plays a crucial role in the proliferation, metastasis, and EMT progression of bladder cancer. Targeting this METTL3-P3H4 pathway may serve as a potential therapeutic strategy for bladder cancer.
CELLULAR SIGNALLING
(2024)