AI Article Synopsis
- Tissue-resident dendritic cells use structures called podosomes to migrate slowly and detect foreign antigens, remodeling the extracellular matrix in the process.
- Podosomes have a core made of actin and an outer ring of proteins that help with adhesion and structure.
- The study reveals that the interplay between actin polymerization, myosin IIA tension, and specific proteins is crucial for maintaining podosome integrity, helping dendritic cells effectively sense their surrounding environment.
Article Abstract
Tissue-resident dendritic cells patrol for foreign antigens while undergoing slow mesenchymal migration. Using actomyosin-based structures called podosomes, dendritic cells probe and remodel extracellular matrix topographical cues. Podosomes comprise an actin-rich protrusive core surrounded by an adhesive ring of integrins, cytoskeletal adaptor proteins and actin network filaments. Here we reveal how the integrity and dynamics of protrusive cores and adhesive rings are coordinated by the actomyosin apparatus. Core growth by actin polymerization induces podosome protrusion and provides tension within the actin network filaments. The tension transmitted to the ring recruits vinculin and zyxin and preserves overall podosome integrity. Conversely, myosin IIA contracts the actin network filaments and applies tension to the vinculin molecules bound, counterbalancing core growth and eventually reducing podosome size and protrusion. We demonstrate a previously unrecognized interplay between actin and myosin IIA in podosomes, providing novel mechanistic insights into how actomyosin-based structures allow dendritic cells to sense the extracellular environment.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3562466 | PMC |
| http://dx.doi.org/10.1038/ncomms2402 | 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 PDFInpp5e Is Critical for Photoreceptor Outer Segment Maintenance.
J Cell Sci
January 2025
Program in Molecular Medicine, University of Massachusetts Chan Medical School, Suite 213 Biotech II, 373 Plantation Street, Worcester MA 01605, USA.
In humans, inositol polyphosphate-5-phosphatase e (INPP5E) mutations cause retinal degeneration as part of Joubert and MORM syndromes and can also cause non-syndromic blindness. In mice, mutations cause a spectrum of brain, kidney, and other anomalies and prevent the formation of photoreceptor outer segments. To further explore the function of Inpp5e in photoreceptors, we generated conditional and inducible knockouts of mouse Inpp5e where the gene was deleted either during outer segment formation or after outer segments were fully formed.
View Article and Find Full Text PDFTBC1D20 coordinates vesicle transport and actin remodeling to regulate ciliogenesis.
J Cell Biol
April 2025
Department of Genetics and Cell Biology, College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China.
TBC1D20 deficiency causes Warburg Micro Syndrome in humans, characterized by multiple eye abnormalities, severe intellectual disability, and abnormal sexual development, but the molecular mechanisms remain unknown. Here, we identify TBC1D20 as a novel Rab11 GTPase-activating protein that coordinates vesicle transport and actin remodeling to regulate ciliogenesis. Depletion of TBC1D20 promotes Rab11 vesicle accumulation and actin deconstruction around the centrosome, facilitating the initiation of ciliogenesis even in cycling cells.
View Article and Find Full Text PDFSuperResNET: Single molecule network analysis detects changes to clathrin structure by small molecule inhibitors.
J Cell Sci
January 2025
Department of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Here, we apply SuperResNET network analysis of dSTORM single-molecule localization microscopy (SMLM) to determine how the clathrin endocytosis inhibitors pitstop 2, dynasore and Latrunculin A alter the morphology of clathrin-coated pits. SuperResNET analysis of HeLa and Cos7 cells identifies: small oligomers (Class I); pits and vesicles (Class II); and larger clusters corresponding to fused pits or clathrin plaques (Class III). Pitstop 2 and dynasore induce distinct homogeneous populations of Class II structures in HeLa cells suggesting that they arrest endocytosis at different stages.
View Article and Find Full Text PDFThe Ca-actin-cytoskeleton axis in podocytes is an important, non-immunologic target of immunosuppressive therapy in proteinuric kidney diseases.
Pediatr Nephrol
January 2025
Department of Pediatrics, University of Cologne, Faculty of Medicine and University Hospital Cologne, Kerpener Street 62, 50937, Cologne, Germany.
The integrity of the filtration barrier of the kidney relies on the proper composition of podocyte interdigitating foot processes. Their architecture is supported by a complex actin-cytoskeleton. Following podocyte stress or injury, podocytes encounter structural changes, including rearrangement of the actin network and subsequent effacement of the foot processes.
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!