Article
Multidisciplinary Sciences
Shuangshuang Zhao, Qiuping Xu, Yanqin Cui, Su Yao, Sihui Jin, Qian Zhang, Zeyu Wen, Haihua Ruan, Xin Liang, Yanjie Chao, Sitang Gong, Philippe Sansonetti, Ke Wei, Hong Tang, Yaming Jiu
Summary: Intracellular bacteria can manipulate the host cytoskeleton to create spaces for replication. The Salmonella effector SopB rearranges the vimentin network to form cage-like structures around the bacteria. Inhibition of MEK1/2 results in vimentin dispersion and disrupts bacterial replication, demonstrating the importance of the SopB-Cdc42-MEK1/2 signaling axis in maintaining stable Salmonella-containing vacuoles.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Kana Asano-Matsuda, Sajida Ibrahim, Tomoko Takano, Jun Matsuda
Summary: The initial step of urine formation involves selective filtration of plasma in the glomerulus, where a filtration barrier made up of three layers (fenestrated endothelial cells, glomerular basement membrane, and podocytes) retains blood cells and large proteins while removing waste products. Rho GTPases serve as crucial molecular switches in regulating podocyte health and barrier function, with particular focus on subcellular compartments where signaling events occur.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemical Research Methods
Erin E. Berlew, Keisuke Yamada, Ivan A. Kuznetsov, Eleanor A. Rand, Chandler C. Ochs, Zaynab Jaber, Kevin H. Gardner, Brian Y. Chow
Summary: In this study, we efficiently created single-component optogenetic tools for membrane recruitment-based signaling perturbation using BcLOV4 technology. Screening a limited set of genetic constructs and observing their dynamic translocation in response to light enabled the identification of viable signaling control tools. We successfully created an optogenetic Cdc42 GTPase and Rac1-activating Tiam1 GEF protein, completing a toolbox for spatiotemporally precise induction of Rho-family GTPase signaling.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Mutsuko Kukimoto-Niino, Kentaro Ihara, Chiemi Mishima-Tsumagari, Mio Inoue, Yoshinori Fukui, Shigeyuki Yokoyama, Mikako Shirouzu
Summary: This study reveals the crystal structures of the catalytic DHR2 domain of mouse DOCK10, complexed with either Cdc42 or Rac1, and uncovers the unique dual activation mechanism of DOCK10.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Cell Biology
Sheila Bandyopadhyay, Xiao Zhang, Andrea Ascura, Karen L. Edelblum, Edward M. Bonder, Nan Gao
Summary: In this study, a novel host regulator of enteric Salmonella infections, CDC42EP1, was identified. It was found that CDC42EP1 interacts with SEPTIN-7 and Villin, and its localization and engagement with bacteria depends on host CDC42 and S. Typhimurium's capability of activating CDC42. CDC42EP1 is not required for S. Typhimurium's initial cellular entry but contributes to the pathogen's intracellular growth and replication.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Review
Neurosciences
Maxsam S. Donta, Yogesh Srivastava, Pierre D. McCrea
Summary: This study explores how delta-catenin modulates small Rho GTPase activity. The regulation of small Rho GTPase activity is crucial for normal learning and memory as well as synapse formation, while dysregulation of delta-catenin is associated with various diseases such as cancer and AD.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
He Sun, Xinlu Zhu, Chuanxi Li, Zhiming Ma, Xiao Han, Yuanyuan Luo, Liang Yang, Jing Yu, Yansong Miao
Summary: The study reveals a mechanism by which bacterial T3Es subvert the host actin cytoskeleton through liquid-liquid phase separation, providing insight into the sophisticated strategies pathogens use to manipulate host cell processes.
NATURE COMMUNICATIONS
(2021)
Review
Cell Biology
Qiaojuan Mei, Huiying Li, Yu Liu, Xiaofei Wang, Wenpei Xiang
Summary: CDC42, a member of the Rho-GTPase family, plays a crucial role in establishing polarity and ensuring proper gametogenesis in female vertebrate oocytes. Through its local occupation of specific regions and synergistic regulation in a multilevel signalling network, CDC42 ensures precise assembly of the contractile ring at the right time and place for accurate gametogenesis.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Vanessa Aline Bernusso, Karla P. Vieira, Adriana S. S. Duarte, Caroline Honaiser Lescano, Fabiola Zakia Monica, Cristina Pontes Vicente, Erich Vinicius De Paula, Sara Teresinha Olalla Saad, Mariana Lazarini
Summary: The RhoGAP protein ARHGAP21 plays a critical role in megakaryocytic differentiation and platelet function by regulating cytoskeletal rearrangement. Silencing of ARHGAP21 affects microtubule stability and cell spreading, while haploinsufficiency of Arhgap21 leads to enhanced platelet activation and thrombus formation. These findings suggest that ARHGAP21 may be a key protein in the control of platelet production and function.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Article
Developmental Biology
Yuko Yoshida, Atsushi Yamada, Yoshihiro Akimoto, Kyoko Abe, Sachie Matsubara, Junri Hayakawa, Junichi Tanaka, Mitsuhiro Kinoshita, Tadashi Kato, Hiroaki Ogata, Akiko Sakashita, Kenji Mishima, Yoshiaki Kubota, Hayato Kawakami, Ryutaro Kamijo, Takehiko Iijima
Summary: Cdc42 plays a critical role in blood vessel formation in vascular endothelial cells, as shown by the abnormal vascular phenotypes in Cdc42 cKO mice and reduced vascular sprouting induced by VEGF-A. Electron microscopy revealed detachment of endothelial cells and macrophage-induced phagocytosis of dead endothelial cells in Cdc42 cKO mice.
DEVELOPMENTAL BIOLOGY
(2021)
Article
Medicine, General & Internal
Gue-Tae Moon, Ji-Hyun Lee, Sang-Hyun Jeong, Song-Wan Jin, Young-Min Park
Summary: This study demonstrated that NX-5 can suppress melanoma metastasis by reducing the expression levels of Rho-family GTPases, including decreasing migration and regulating the expression of related proteins.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Vishnu Priyanka Reddy Chichili, Ti Weng Chew, Srihari Shankar, Shi Yin Er, Cheen Fei Chin, Chacko Jobichen, Catherine Qiurong Pan, Yiting Zhou, Foong May Yeong, Boon Chuan Low, J. Sivaraman
Summary: The spatiotemporal regulation of signaling cascades is essential for various biological pathways and is controlled by scaffolding proteins. The BCH domain targets small GTPases and their regulators, playing a crucial role in cell elongation, retraction, and membrane protrusion during cell migration, myoblast differentiation, and neuritogenesis. Analysis of the BCH domain of p50RhoGAP revealed a dimeric structure with unique RhoA-binding loop and lipid-binding pocket, providing insights into the regulation of Rho activity. Additionally, a destabilizing mutation in the BCH domain triggers the release of the adjacent GAP domain, leading to RhoA inactivation and increased self-association of p50RhoGAP molecules.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Anthony J. Asmar, Shaun R. Abrams, Jenny Hsin, Jason C. Collins, Rita M. Yazejian, Youmei Wu, Jean Cho, Andrew D. Doyle, Samhitha Cinthala, Marleen Simon, Richard H. van Jaarsveld, David B. Beck, Laura Kerosuo, Achim Werner
Summary: This study uncovers a posttranslational pathway that controls cytoskeletal signaling circuits to coordinate ectodermal patterning and neurulation. A specific tissue-specific restriction of CDC42 signaling by a ubiquitin-based effector-to-inhibitor is essential for early face, brain, and skin formation. Loss of this pathway leads to defective ectodermal patterning and neurulation.
NATURE COMMUNICATIONS
(2023)
Article
Microbiology
Oceane Dufies, Laurent Boyer
Summary: Pathogens have evolved smart strategies to invade hosts by targeting host RhoGTPases, controlling cytoskeleton dynamics and immune processes; hosts monitor the function of virulence factors and toxins through sensing the abnormal activity of RhoGTPases; hosts can sense the activity of toxins through NOD and NOD-like receptors (NLRs).
Article
Cell Biology
Eike K. Mahlandt, Gabriel Kreider-Letterman, Anna O. Chertkova, Rafael Garcia-Mata, Joachim Goedhart
Summary: In this study, relocation sensor candidates for Rac and Cdc42 were identified and their efficiency was improved using a multi-domain approach. Optimized sensors for Cdc42 were found to have sufficient relocation efficiency and specificity. These findings enable the wider application of Rho GTPase relocation sensors and were showcased by the detection of local endogenous Cdc42 activity at assembling invadopodia. The characterization and optimization of relocation sensors will broaden their application and acceptance.
JOURNAL OF CELL SCIENCE
(2023)
Article
Biochemical Research Methods
Michael D. Rush, Elisabeth M. Walker, Gerd Prehna, Tristesse Burton, Richard B. van Breemen
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2017)
Article
Biochemistry & Molecular Biology
Laty A. Cahoon, Nancy E. Freitag, Gerd Prehna
MOLECULAR MICROBIOLOGY
(2016)
Article
Microbiology
Antoine Talagas, Laetitia Fontaine, Laura Ledesma-Garca, Johann Mignolet, Ines Li de la Sierra-Gallay, Noureddine Lazar, Magali Aumont-Nicaise, Michael J. Federle, Gerd Prehna, Pascal Hols, Sylvie Nessler
Article
Microbiology
Erin Shanker, Donald A. Morrison, Antoine Talagas, Sylvie Nessler, Michael J. Federle, Gerd Prehna
Article
Biochemistry & Molecular Biology
Matthew Solomonson, Pitter F. Huesgen, Gregory A. Wasney, Nobuhiko Watanabe, Robert J. Gruninger, Gerd Prehna, Christopher M. Overall, Natalie C. J. Strynadka
JOURNAL OF BIOLOGICAL CHEMISTRY
(2013)
Article
Multidisciplinary Sciences
Gerd Prehna, Benjamin E. Ramirez, Andrew L. Lovering
Article
Microbiology
Tamiko Oguri, Youjeong Kwon, Jerry K. K. Woo, Gerd Prehna, Hyun Lee, Miaoran Ning, Kyoung-Jae Won, Jiyoung Lee, Sally Mei, Yixin Shi, Hyunyoung Jeong, Hyunwoo Lee
JOURNAL OF BACTERIOLOGY
(2019)
Article
Multidisciplinary Sciences
Lauren Mashburn-Warren, Steven D. Goodman, Michael J. Federle, Gerd Prehna
SCIENTIFIC REPORTS
(2018)
Article
Biochemistry & Molecular Biology
Nicole L. Inniss, Gerd Prehna, Donald A. Morrison
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Biology
Shehryar Ahmad, Kara K. Tsang, Kartik Sachar, Dennis Quentin, Tahmid M. Tashin, Nathan P. Bullen, Stefan Raunser, Andrew G. McArthur, Gerd Prehna, John C. Whitney
Article
Biochemistry & Molecular Biology
Nicole R. Rutbeek, Hanieh Rezasoltani, Trushar R. Patel, Mazdak Khajehpour, Gerd Prehna
Summary: Streptococcus pyogenes inhibits its quorum sensing receptor ComR through the phage-encoded Prx protein, affecting its uptake of exogenous DNA. This mechanism is similar to the role of the phage protein Aqs1 in Pseudomonas aeruginosa in inhibiting quorum sensing, demonstrating a convergent evolution between Gram-positive and Gram-negative phages in quorum sensing inhibition.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Microbiology
Elizabeth J. Culp, David Sychantha, Christian Hobson, Andrew C. Pawlowski, Gerd Prehna, Gerard D. Wright
Summary: A widespread family of bacterial ClpP-associated gene clusters has been identified, which produce specific compounds that selectively inhibit ClpP enzyme activity and may play an important role in bacterial competition.
NATURE MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Neil Lorente Cobo, Stephanie Sibinelli-Sousa, Jacob Biboy, Waldemar Vollmer, Ethel Bayer-Santos, Gerd Prehna
Summary: This study reveals the structure and function of the T6SS effector Tlde1a from Salmonella Typhimurium. Tlde1a possesses a unique LD-transpeptidase fold, which is structurally altered to create its toxic effect and plays an important role in bacterial competition.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Nathan P. Bullen, David Sychantha, Stephanie S. Thang, Peter H. Culviner, Marta Rudzite, Shehryar Ahmad, Vraj S. Shah, Alain Filloux, Gerd Prehna, John C. Whitney
Summary: ADP-ribosyltransferases (ARTs) are bacterial virulence factors that modify essential proteins to promote pathogenesis. This study reports the discovery of RhsP2 as an ART toxin delivered by a type VI secretion system. RhsP2 can ADP-ribosylate double-stranded RNA, leading to inhibition of translation and disruption of tRNA processing, ultimately causing cell death. This finding uncovers a previously unknown mechanism of bacterial antagonism and highlights the unprecedented activity of ART enzymes.
Article
Biochemistry & Molecular Biology
Gaurang P. Bhide, Gerd Prehna, Benjamin E. Ramirez, Karen J. Colley