Extracellular cues that regulate cellular shape, motility, and navigation are generally classified as growth promoting (i.e., growth factors/chemoattractants and attractive guidance cues) or growth preventing (i.e., repellents and inhibitors). Yet, these designations are often based on complex assays and undefined signaling pathways and thus may misrepresent direct roles of specific cues. Here, we find that a recognized growth-promoting signaling pathway amplifies the F-actin disassembly and repulsive effects of a growth-preventing pathway. Focusing on Semaphorin/Plexin repulsion, we identified an interaction between the F-actin-disassembly enzyme Mical and the Abl tyrosine kinase. Biochemical assays revealed Abl phosphorylates Mical to directly amplify Mical Redox-mediated F-actin disassembly. Genetic assays revealed that Abl allows growth factors and Semaphorin/Plexin repellents to combinatorially increase Mical-mediated F-actin disassembly, cellular remodeling, and repulsive axon guidance. Similar roles for Mical in growth factor/Abl-related cancer cell behaviors further revealed contexts in which characterized positive effectors of growth/guidance stimulate such negative cellular effects as F-actin disassembly/repulsion.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564210 | PMC |
| http://dx.doi.org/10.1016/j.devcel.2017.06.007 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The open to closed D-loop conformational switch determines length in filopodia-like actin bundles.
Biochem J
December 2024
Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, U.K.
Article Synopsis
- Filopodia, microspikes, and cytonemes are structures in cells that help sense the environment and transport various materials across tissues, built mainly from bundles of actin filaments.
- The study discovered monoclonal antibodies that can elongate filopodia-like structures by targeting a specific part of actin filaments known as the D-loop.
- By preventing actin disassembly, these antibodies provide insights into how the length of filopodia is regulated, suggesting that keeping the actin filament D-loop in an open state promotes longer structures.
HIV-1 budding requires cortical actin disassembly by the oxidoreductase MICAL1.
Proc Natl Acad Sci U S A
November 2024
Membrane Traffic and Cell Division Unit, Institut Pasteur, Université Paris Cité, CNRS UMR3691, Paris F-75015, France.
Many enveloped viruses bud from the plasma membrane that is tightly associated with a dense and thick actin cortex. This actin network represents a significant challenge for membrane deformation and scission, and how it is remodeled during the late steps of the viral cycle is largely unknown. Using superresolution microscopy, we show that HIV-1 buds in areas of the plasma membrane with low cortical F-actin levels.
View Article and Find Full Text PDFBisphenol A disrupts the neuronal F-actin cytoskeleton by activating the RhoA/ROCK/LIMK pathway in Neuro-2a cells.
Toxicology
December 2024
Medical Experiment Center, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712046, China; Key Laboratory of Environment-related Diseases and TCM Prevention and Control in Universities of Shaanxi Province, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712046, China. Electronic address:
Bisphenol A (BPA) is an environmental endocrine disruptor that is widely present in the environment and has been reported to affect neuronal cytoskeleton and neural function. However, the exact molecular mechanisms remain unclear. In the present study, the effects of BPA on cytoskeleton rearrangement were examined, and the associated signaling pathways, which were influenced by the RhoA/ROCK/LIMK pathway in Neuro-2a cells in vitro, were identified.
View Article and Find Full Text PDFDecoupling actin assembly from microtubule disassembly by TBC1D3C-mediated direct GEF-H1 activation.
Life Sci Alliance
January 2025
Clinical Systems Biology Laboratories, Translational Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Actin and microtubules are essential cytoskeletal components and coordinate their dynamics through multiple coupling and decoupling mechanisms. However, how actin and microtubule dynamics are decoupled remains incompletely understood. Here, we identified TBC1D3C as a new regulator that can decouple actin filament assembly from microtubule disassembly.
View Article and Find Full Text PDFCHK1 controls zygote pronuclear envelope breakdown by regulating F-actin through interacting with MICAL3.
EMBO Rep
November 2024
Institute of Women, Children and Reproductive Health, Shandong University, 250012, Jinan, China.
CHK1 mutations could cause human zygote arrest at the pronuclei stage, a phenomenon that is not well understood at the molecular level. In this study, we conducted experiments where pre-pronuclei from zygotes with CHK1 mutation were transferred into the cytoplasm of normal enucleated fertilized eggs. This approach rescued the zygote arrest caused by the mutation, resulting in the production of a high-quality blastocyst.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!