Background: Actin remodeling is a key regulator of mast cell (MC) migration and secretion. However, the precise mechanism underlying the coordination of these processes has remained obscure.
Objective: We sought to characterize the actin rearrangements that occur during MC secretion or chemotactic migration and identify the underlying mechanism of their coordination.
Methods: Using high-resolution microscopy, we analyzed the dynamics of actin rearrangements in MCs triggered to migration by IL-8 or prostaglandin E or to FcεRI-stimulated secretion.
Results: We show that a major feature of the actin skeleton in MCs stimulated to migration is the buildup of pericentral actin clusters that prevent cell flattening and converge the secretory granules (SGs) in the cell center. This migratory phenotype is replaced on encounter of an IgE cross-linking antigen that stimulates secretion through a secretory phenotype characterized by cell flattening, reduction of actin mesh density, ruffling of cortical actin, and mobilization of SGs. Furthermore, we show that knockdown of mammalian diaphanous-related formin 1 (mDia1) inhibits chemotactic migration and its typical actin rearrangements, whereas expression of an active mDia1 mutant recapitulates the migratory actin phenotype and enhances cell migration while inhibiting FcεRI-triggered secretion. However, mice deficient in mDia1 appear to have normal numbers of MCs in various organs at baseline.
Conclusion: Our results demonstrate a unique role of actin rearrangements in clustering the SGs and inhibiting their secretion during MC migration. We identify mDia1 as a novel regulator of MC response that coordinates MC chemotaxis and secretion through its actin-nucleating activity.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278082 | PMC |
| http://dx.doi.org/10.1016/j.jaci.2019.06.028 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Stem cells adapt to their local mechanical environment by rearranging their cytoskeleton, which underpins the evolution of their shape and fate as well as the emergence of tissue structure and function. Here, in the second part of a two-part experimental series, we aimed to elucidate spatiotemporal cytoskeletal remodeling and resulting changes in morphology and mechanical properties of cells and their nuclei. Akin to mechanical testing of the most basic living and adapting unit of life, i.
View Article and Find Full Text PDFCryo-EM reconstruction of yeast ADP-actin filament at 2.5 Å resolution. A comparison with vertebrate F-actin.
Structure
January 2025
Molecular Microbiology, School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK. Electronic address:
The core component of the actin cytoskeleton is the globular protein G-actin, which reversibly polymerizes into filaments (F-actin). Budding yeast possesses a single actin that shares 87%-89% sequence identity with vertebrate actin isoforms. Previous structural studies indicate very close overlap of main-chain backbones.
View Article and Find Full Text PDFSTIPS algorithm enables tracking labyrinthine patterns and reveals distinct rhythmic dynamics of actin microridges.
Phys Biol
January 2025
Department of Biological Sciences, Tata Institute of Fundamental Research Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha road, Navy Nagar, Colaba, Mumbai-400005, INDIA, Mumbai, 400005, INDIA.
Tracking and motion analyses of semi-flexible biopolymer networks from time-lapse microscopy images are important tools that enable quantitative measurements to unravel the dynamic and mechanical properties of biopolymers in living tissues, crucial for understanding their organization and function. Biopolymer networks are challenging to track due to continuous stochastic transitions, such as merges and splits, which cause local neighbourhood rearrangements over short time and length scales. To address this, we propose the STIPS algorithm (Spatio Temporal Information on Pixel Subsets) to track these events by creating pixel subsets that link trajectories across frames.
View Article and Find Full Text PDFSodium arsenite induces islets β-cells apoptosis and dysfunction via SET-Rac1-mediated cytoskeleton disturbance.
Ecotoxicol Environ Saf
January 2025
Department of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, China; Global Health Research Center, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, China. Electronic address:
Sodium arsenite (NaAsO), the most common form of inorganic arsenic prevalent in the environment, has been closely linked to islet β-cell dysfunction, a critical pathological hallmark of type 2 diabetes (T2D). Even though apoptosis plays a pivotal role in arsenic-induced islet β-cell dysfunction, the explicit underlying mechanisms remain elusive. Here, we have identified that the SET-Rac1 signaling pathway is instrumental in the apoptosis and dysfunction of islet β-cells induced by NaAsO.
View Article and Find Full Text PDFFAK inhibition delays liver repair after acetaminophen-induced acute liver injury by suppressing hepatocyte proliferation and macrophage recruitment.
Hepatol Commun
November 2024
Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China.
Background: Overdose of acetaminophen (APAP), a commonly used antipyretic analgesic, can lead to severe liver injury and failure. Current treatments are only effective in the early stages of APAP-induced acute liver injury (ALI). Therefore, a detailed examination of the mechanisms involved in liver repair following APAP-induced ALI could provide valuable insights for clinical interventions.
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!