Article
Multidisciplinary Sciences
William J. Spencer, Nicholas F. Schneider, Tylor R. Lewis, Carson M. Castillo, Nikolai P. Skiba, Vadim Y. Arshavsky
Summary: The photoreceptor outer segment is a cilium filled with flat-tened disc membranes for light capture. The addition of new discs at the base of outer segments is driven by Arp2/3-mediated actin polymerization initiated by the pentameric WAVE complex. Knockout of WASF3, a subunit of the WAVE complex, disrupts actin polymerization and leads to disorganized membrane lamellae instead of a proper outer segment.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Bojian Ding, Heidy Y. Narvaez-Ortiz, Yuvraj Singh, Glen M. Hocky, Saikat Chowdhury, Brad J. Nolen
Summary: Arp2/3 complex nucleates branched actin filaments and provides pushing forces for cellular processes. This study reveals the contacts between Arp2/3 complex and the mother actin filament, suggesting that actin filaments stimulate subunit flattening for complex activation. However, limited contact between the bottom half of the complex and the mother filament may explain why actin filaments are required but insufficient to trigger nucleation during WASP-mediated activation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Luyan Cao, Foad Ghasemi, Michael Way, Antoine Jegou, Guillaume Romet-Lemonne
Summary: Activation of the Arp2/3 complex by actin nucleation-promoting factors leads to the formation of branching actin filaments, while direct nucleation of linear actin filaments is induced by SPIN90-Arp2/3. Interestingly, the VCA motifs of certain proteins destabilize existing branches and linear filament ends. However, branch stabilizer cortactin and destabilizer GMF have similar effects on SPIN90-activated Arp2/3. These findings highlight the importance of understanding the similarities and differences between the two mechanisms in regulating actin cytoskeleton dynamics, as well as the differential responses of branched and linear filaments to aging and mechanical stress.
Article
Cell Biology
Shuting Zhang, Dimitrios Vavylonis
Summary: The nucleation of actin filament branches by the Arp2/3 complex involves activation through nucleation promotion factors (NPFs), recruitment of actin monomers, and binding of the complex to the side of actin filaments. Our molecular dynamics simulations using a coarse-grained model revealed stable configurations of the Arp2/3 complex with actin monomers and the activating VCA domain of the NPF Wiskott-Aldrich syndrome protein, supporting prior structural studies and providing insight into mechanisms proposed in previous studies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Cell Biology
Ruixin Ge, Minghui Cao, Miao Chen, Min Liu, Songbo Xie
Summary: Primary cilia function as sensory organelles that monitor extracellular signals and transduce them into intracellular responses. Actin and microtubule networks play critical roles in primary ciliogenesis and maintenance. Targeting cytoskeleton-associated proteins may be a promising therapeutic strategy for treating ciliopathies.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Artem I. Fokin, Roman N. Chuprov-Netochin, Alexander S. Malyshev, Stephane Romero, Marina N. Semenova, Leonid D. Konyushkin, Sergey V. Leonov, Victor V. Semenov, Alexis M. Gautreau
Summary: Several compounds structurally related to CK-666 were found to suppress Arp2/3 activation, and two of them demonstrated improved in vivo efficiency compared to CK-666.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Cell Biology
Emmanuel Martin, Magali Suzanne
Summary: This review discusses the role of the actin nucleation complex Arp2/3 in epithelial tissue, including its influence on cell-cell cooperation and tissue morphogenesis. It plays a significant role in regulating cell-cell adhesion, intracellular trafficking, and protrusion formation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Neurosciences
Tylor R. Lewis, Mustafa S. Makia, Carson M. Castillo, Muayyad R. Al-Ubaidi, Muna Naash, Vadim Y. Arshavsky
Summary: Mutations in the PRPH2 gene cause a broad range of retinal diseases by affecting the structure of outer segment of photoreceptor cells, resulting in irregular disc enclosure process. Abnormal PRPH2 oligomerization leads to defects in outer segment structure, particularly at the stage of disc enclosure.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Pharmacology & Pharmacy
Coralie Mergault, Fanny Lisee, Victor Tiroille, Melia Magnien, Christelle Parent, Woodys Lenga Mabonda, Damien Sizaret, Madeleine Jaillet, Bruno Crestani, Sylvain Marchand-Adam, Laurent Plantier
Summary: The study found that the expression of the Arp2/3 complex was increased in profibrotic environments in vitro and in vivo. Inhibition of the Arp2/3 complex repressed ACTA2 and COL1 expression and blocked the Akt/phospho-GSK3 beta/beta-catenin/MRTF-A pathway in lung fibroblasts. CK666 demonstrated antifibrotic properties in the lung in vivo.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Marcel Hahn, Adriana Covarrubias-Pinto, Lina Herhaus, Shankha Satpathy, Kevin Klann, Keith B. Boyle, Christian Munch, Krishnaraj Rajalingam, Felix Randow, Chunaram Choudhary, Ivan Dikic
Summary: SIK2 kinase is a central component of the host defense machinery during Salmonella infection, and its depletion can lead to bacterial escape and impaired Xenophagy. During bacterial infection, SIK2 associates with actin and is recruited to the Salmonella-containing vacuole, controlling the formation of a protective SCV actin shield.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Microbiology
Autumn Paluck, Jaspreet Osan, Lauren Hollingsworth, Sattya Narayan Talukdar, Ali Al Saegh, Masfique Mehedi
Summary: RSV is a major viral factor causing pneumonia in children worldwide. The virus interacts with the host actin cytoskeleton, particularly the ARP2/3 complex, to facilitate its replication and spread. Understanding the modulation of the cytoskeleton by RSV and its role in lung pathobiology may lead to novel intervention strategies.
Article
Agriculture, Dairy & Animal Science
Meng-Hao Pan, Rui Xu, Yiqian Zhang, Lu Yin, Ruoyu Li, Dongxu Wen, Sihai Lu, Yan Gao, Xiaoe Zhao, Qiang Wei, Bin Han, Baohua Ma
Summary: Our study demonstrates that the Arp2/3 complex is essential for maintaining cytoskeletal dynamics and mitochondrial function during goat oocyte maturation. Disruption of the Arp2/3 complex leads to impaired F-actin assembly, spindle organization, ROS accumulation, and increased early apoptosis in goat oocytes.
Article
Plant Sciences
Morgan Moser, Norman R. Groves, Iris Meier
Summary: Linker of nucleoskeleton and cytoskeleton (LINC) complexes, consisting of KASH and SUN proteins, connect the nucleus and cytoskeleton. Arabidopsis KASH proteins SINE1 and SINE2 play important roles in stomatal dynamics and plant development, genetically interacting with actin-remodeling factor SCAB1 and the ARP2/3 complex.
JOURNAL OF EXPERIMENTAL BOTANY
(2023)
Article
Multidisciplinary Sciences
Steven Z. Chou, Moon Chatterjee, Thomas D. Pollard
Summary: By analyzing the images collected by electron cryo-microscopy, we reconstructed the structure of actin filament branch junctions formed by fission yeast Arp2/3 complex. The formation of this structure requires a conformational change of the Arp2/3 complex and the acquisition of a new buried surface area to maintain the stability of the branch.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Elsa Ronzier, Alexander J. Laurenson, Rohini Manickam, Sophia Liu, Imelda M. Saintilma, Dillon C. Schrock, John A. Hammer, Jeremy D. Rotty
Summary: The macrophage actin cytoskeleton responds to LPS/IFN-gamma stimulation in a biphasic manner, involving cellular contraction followed by cellular spreading. Myosin II inhibition blocks the initial contraction phase and lowers iNOS protein levels and nitric oxide secretion, while conditional deletion of Arp2/3 complex attenuates spreading and increases nitric oxide secretion. These findings suggest that the interplay between myosin II and Arp2/3 influences macrophage activity and potentially impacts immune coordination.
Article
Neurosciences
Tylor R. Lewis, Mustafa S. Makia, Mashal Kakakhel, Muayyad R. Al-Ubaidi, Vadim Y. Arshavsky, Muna Naash
FRONTIERS IN CELLULAR NEUROSCIENCE
(2020)
Article
Multidisciplinary Sciences
Tylor R. Lewis, Camilla R. Shores, Martha A. Cady, Ying Hao, Vadim Y. Arshaysky, Marie E. Burns
SCIENTIFIC REPORTS
(2020)
Article
Multidisciplinary Sciences
Rupalatha Maddala, Junyuan Gao, Richard T. Mathias, Tylor R. Lewis, Vadim Y. Arshavsky, Adriana Levine, Jonathan M. Backer, Anne R. Bresnick, Ponugoti Rao
Summary: The study demonstrates that S100A4 expression is induced in the differentiating fiber cells of the ocular lens, with its knockout leading to late-onset cortical cataracts and upregulation of photoreceptor- and Muller glia-specific genes. Transcriptome profiling of lenses from S100A4((-/-)) mice revealed changes in histone methylation levels, potentially suggesting a mechanism through which S100A4 suppresses the expression of retinal genes.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Tylor R. Lewis, Mustafa S. Makia, Carson M. Castillo, Muayyad R. Al-Ubaidi, Muna Naash, Vadim Y. Arshavsky
Summary: Mutations in the PRPH2 gene cause a broad range of retinal diseases by affecting the structure of outer segment of photoreceptor cells, resulting in irregular disc enclosure process. Abnormal PRPH2 oligomerization leads to defects in outer segment structure, particularly at the stage of disc enclosure.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Biochemical Research Methods
Nikolai P. Skiba, Martha A. Cady, Laurie Molday, John Y. S. Han, Tylor R. Lewis, William J. Spencer, Will J. Thompson, Sarah Hiles, Nancy J. Philp, Robert S. Molday, Vadim Y. Arshavsky
Summary: The outer segment (OS) organelle of vertebrate photoreceptors is a highly specialized cilium evolved to capture light and initiate light response. The plasma membrane which envelopes the OS plays vital and diverse roles in supporting photoreceptor function and health. In this study, unique OS plasma membrane proteins were identified using protein correlation profiling, revealing several previously unknown membrane proteins.
MOLECULAR & CELLULAR PROTEOMICS
(2021)
Article
Multidisciplinary Sciences
George Khelashvili, Anoop Narayana Pillai, Joon Lee, Kalpana Pandey, Alexander M. Payne, Zarek Siegel, Michel A. Cuendet, Tylor R. Lewis, Vadim Y. Arshavsky, Johannes Broichhagen, Joshua Levitz, Anant K. Menon
Summary: By using fluorescence-based assays and molecular dynamics simulations, it was found that the F220C opsin mutant fails to dimerize in vitro but forms an energetically favored dimer in the plasma membrane of HEK293 cells, with a unique conformation. This unusual mode of dimerization may have physiological consequences.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Tylor R. Lewis, Sebastien Phan, Keun-Young Kim, Isha Jha, Carson M. Castillo, Jin-Dong Ding, Benjamin S. Sajdak, Dana K. Merriman, Mark H. Ellisman, Vadim Y. Arshavsky
Summary: This study reveals that healthy mammalian photoreceptor cells release microvesicles, some of which contain visual pigment rhodopsin. This release may be enhanced under pathological conditions associated with defects in protein targeting and trafficking.
DISEASE MODELS & MECHANISMS
(2022)
Article
Multidisciplinary Sciences
William J. Spencer, Nicholas F. Schneider, Tylor R. Lewis, Carson M. Castillo, Nikolai P. Skiba, Vadim Y. Arshavsky
Summary: The photoreceptor outer segment is a cilium filled with flat-tened disc membranes for light capture. The addition of new discs at the base of outer segments is driven by Arp2/3-mediated actin polymerization initiated by the pentameric WAVE complex. Knockout of WASF3, a subunit of the WAVE complex, disrupts actin polymerization and leads to disorganized membrane lamellae instead of a proper outer segment.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Larissa Ikelle, Mustafa Makia, Tylor Lewis, Ryan Crane, Mashal Kakakhel, Shannon M. Conley, James R. Birtley, Vadim Y. Arshavsky, Muayyad R. Al-Ubaidi, Muna I. Naash
Summary: Mutations in the PRPH2 gene can lead to retinal degeneration. Contrary to previous understanding, new research reveals that these mutations affect PRPH2 function by interfering with oligomerization, resulting in highly affected rod cells and less affected cone cells. This finding is important for the development of therapeutic approaches for PRPH2-associated diseases.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemical Research Methods
Nikolai P. P. Skiba, Tylor R. R. Lewis, William J. J. Spencer, Carson M. M. Castillo, Andrej Shevchenko, Vadim Y. Y. Arshavsky
Summary: We used quantitative mass spectrometry to determine the abundances of 20 key proteins in mouse rod outer segments, and calculated the absolute number of molecules and molar ratios for each protein. This study resolved discrepancies in the reported abundances of these proteins and advanced our understanding of the coordinated molecular function of the phototransduction pathway.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Biology
Tylor R. Lewis, Sebastien Phan, Carson M. Castillo, Keun-Young Kim, Kelsey Coppenrath, William Thomas, Ying Hao, Nikolai P. Skiba, Marko E. Horb, Mark H. Ellisman, Vadim Y. Arshavsky, Audrey M. Bernstein
Summary: The initial steps of vision occur in stacked membrane structures called discs located within the outer segment compartment of photoreceptor cells. These discs become enclosed and form deep indentations known as incisures. Using electron microscopy and tomography, it was discovered that incisures only form after complete disc enclosure. The size of the incisures is determined by the ratio of peripherin-2 to rhodopsin, with a higher ratio resulting in larger and more complex incisures.
Article
Cell Biology
Christopher C. Pan, Raquel Maeso-Diaz, Tylor R. Lewis, Kun Xiang, Lianmei Tan, Yaosi Liang, Liuyang Wang, Fengrui Yang, Tao Yin, Calvin Wang, Kuo Du, De Huang, Seh Hoon Oh, Ergang Wang, Bryan Jian Wei Lim, Mengyang Chong, Peter B. Alexander, Xuebiao Yao, Vadim Y. Arshavsky, Qi-Jing Li, Anna Mae Diehl, Xiao-Fan Wang
Summary: Cellular senescence is a stable cell cycle arrest phenotype induced by stress, which creates a pro-inflammatory microenvironment and contributes to chronic inflammation and age-associated diseases. The molecular pathway involving thrombomodulin (THBD) signaling plays a crucial role in determining the fate of senescent cells, and inhibiting this pathway can effectively eliminate senescent cells and restore tissue homeostasis. These findings provide a potential target for developing senolytic agents to treat senescence-associated diseases.
Review
Cell Biology
William J. Spencer, Tylor R. Lewis, Jillian N. Pearring, Vadim Y. Arshavsky
TRENDS IN CELL BIOLOGY
(2020)