Dendritic cells (DCs) flexibly adapt to different microenvironments by using diverse migration strategies that are ultimately dependent on the dynamics and structural organization of the actin cytoskeleton. Here, we have shown that DCs require the actin capping activity of the signaling adaptor Eps8 to polarize and to form elongated migratory protrusions. DCs from Eps8-deficient mice are impaired in directional and chemotactic migration in 3D in vitro and are delayed in reaching the draining lymph node (DLN) in vivo after inflammatory challenge. Hence, Eps8-deficient mice are unable to mount a contact hypersensitivity response. We have also shown that the DC migratory defect is cell autonomous and that Eps8 is required for the proper architectural organization of the actin meshwork and dynamics of cell protrusions. Yet, Eps8 is not necessary for antigen uptake, processing, and presentation. Thus, we have identified Eps8 as a unique actin capping protein specifically required for DC migration.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3424277 | PMC |
| http://dx.doi.org/10.1016/j.immuni.2011.07.007 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The actin filament pointed-end depolymerase Srv2/CAP depolymerizes barbed ends, displaces capping protein, and promotes formin processivity.
Proc Natl Acad Sci U S A
February 2025
Departments of Physics, Cell Biology and Biochemistry, Emory University, Atlanta, GA 30322.
Cellular actin networks exhibit distinct assembly and disassembly dynamics, primarily driven by multicomponent reactions occurring at the two ends of actin filaments. While barbed ends are recognized as the hotspot for polymerization, depolymerization is predominantly associated with pointed ends. Consequently, mechanisms promoting barbed-end depolymerization have received relatively little attention.
View Article and Find Full Text PDFStructural insights into actin filament turnover.
Trends Cell Biol
January 2025
Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany. Electronic address:
The dynamic turnover of actin filaments drives the morphogenesis and migration of all eukaryotic cells. This review summarizes recent insights into the molecular mechanisms of actin polymerization and disassembly obtained through high-resolution structures of actin filament assemblies. We first describe how, upon polymerization, actin subunits age within the filament through changes in their associated adenine nucleotide.
View Article and Find Full Text PDFRegulation of actin dynamics by Twinfilin.
Curr Opin Cell Biol
February 2025
Departments of Physics, Cell Biology and Biochemistry, Emory University, Atlanta, GA 30322, USA. Electronic address:
Twinfilin is an evolutionarily conserved actin-binding protein initially mischaracterized as a tyrosine kinase but later recognized as a key regulator of cellular actin dynamics. As a member of the ADF-H family, twinfilin binds both actin monomers and filaments. Its role in sequestering G-actin is well-established, but its effects on actin filaments have been debated.
View Article and Find Full Text PDFA truncated isoform of Connexin43 caps actin to organize forward delivery of full-length Connexin43.
J Cell Biol
March 2025
Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, USA.
While membrane proteins such as ion channels continuously turn over and require replacement, the mechanisms of specificity of efficient channel delivery to appropriate membrane subdomains remain poorly understood. GJA1-20k is a truncated Connexin43 (Cx43) isoform arising from translation initiating at an internal start codon within the same parent GJA1 mRNA and is requisite for full-length Cx43 trafficking to cell borders. GJA1-20k does not have a full transmembrane domain, and it is not known how GJA1-20k enables forward delivery of Cx43 hemichannels.
View Article and Find Full Text PDFCytoskeleton Remodeling-Related Proteins Represent a Specific Salivary Signature in PSC Patients.
Molecules
December 2024
Institute of Clinical Physiology, National Research Council, 56124 Pisa, Italy.
Article Synopsis
- - Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are chronic liver diseases that damage bile ducts and lead to liver fibrosis and cirrhosis, but no specific biomarkers exist to differentiate them.
- - This study analyzed saliva samples from 6 PBC patients using advanced mass spectrometry, comparing the results with samples from PSC patients, and identified 40 proteins that were significantly deregulated in PSC.
- - The research revealed that some of these proteins are involved in immune responses and cytoskeleton remodeling, suggesting that saliva could be a valuable source for discovering biomarkers to differentiate between PSC and PBC.
Want 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!