Cell motility entails the reorganization of the cytoskeleton and membrane trafficking for effective protrusion. GIT1/p95-APP1 is a member of a family of GTPase-activating proteins for ARF GTPases that affect endocytosis, adhesion and migration. GIT1 associates with paxillin and a complex including the Rac/Cdc42 exchanging factors PIX/Cool and the kinase PAK. In this study, we show that overexpression of betaPIX induces the accumulation of endogenous and overexpressed GIT1 at large structures similar to those induced by an ArfGAP-defective mutant of GIT1 (p95-C2). Immunohistochemical analysis and immunoelectron microscopy reveal that these structures include the endogenous transferrin receptor. Time-lapse analysis during motogenic stimuli shows that the formation and perinuclear accumulation of the p95-C2-positive structures is paralleled by inhibition of lamellipodium formation and cell retraction. Both dimerization and a functional SH3 domain of betaPIX are required for the accumulation of GIT1 in fibroblasts, which is prevented by the monomeric PIX-PG-DeltaLZ. This mutant also prevents the formation of endocytic aggregates and inhibition of neurite outgrowth in retinal neurons expressing p95-C2. Our results indicate that betaPIX is an important regulator of the subcellular distribution of GIT1, and suggest that alteration in the level of expression of the complex affects the endocytic compartment and cell motility.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1242/jcs.02996 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Effect of age-associated oxidative stress on sperm viability, acrosomal integrity and sperm apoptosis and DNA fragmentation in Sahiwal breeding bulls.
Vet Res Commun
January 2025
ARGO, ICAR- National Dairy Research Institute, Deemed University, Karnal, India.
Sperm motility is the prime functional attribute for semen quality and fertility of the bull. However, the bull's age directly affects the semen quality, and the bull's fertility and productive life decline with age. Even though research on age has been conducted in the past, it is still unclear how old a bull should be maintained at artificial insemination centers.
View Article and Find Full Text PDFEnhancing Corneal Sensitivity in Diabetic Patients Through an Innovative Ophthalmic Solution: In Vivo and Vitro Results.
J Clin Med
January 2025
Department of Sciences, Section of Biomedical Sciences and Technologies, Roma Tre University, Viale Marconi 446, 00146 Rome, Italy.
: Diabetes is a well-recognised factor inducing a plethora of corneal alterations ranging from dry eye to reduced corneal sensibility, epithelial defects, and reduced cicatrisation. This cohort study aimed to assess the efficacy of a novel ophthalmic solution combining cross-linked hyaluronic acid (CHA), chondroitin sulfate (CS), and inositol (INS) in managing diabetes-induced corneal alterations. Specifically, it evaluated the solution's impact on the tear breakup time (TBUT), the ocular surface disease index (OSDI), and corneal sensitivity after three months of treatment.
View Article and Find Full Text PDFThe Vimentin-Targeting Drug ALD-R491 Partially Reverts the Epithelial-to-Mesenchymal Transition and Vimentin Interactome of Lung Cancer Cells.
Cancers (Basel)
December 2024
Department of Oncology-Pathology, Karolinska Institutet, 171 64 Solna, Sweden.
The epithelial-to-mesenchymal transition (EMT) is a common feature in early cancer invasion. Increased vimentin is a canonical marker of the EMT; however, the role of vimentin in EMT remains unknown. To clarify this, we induced EMT in lung cancer cells with TGF-β1, followed by treatment with the vimentin-targeting drug ALD-R491, live-cell imaging, and quantitative proteomics.
View Article and Find Full Text PDFOptimized Spheroid Model of Pancreatic Cancer Demonstrates Influence of Macrophage-T Cell Interaction for Intratumoral T Cell Motility.
Cancers (Basel)
December 2024
Department of Gastroenterology, Endocrinology, Infectious Diseases and Metabolism, University Hospital Marburg, 35043 Marburg, Germany.
Background: Most spheroid models use size measurements as a primary readout parameter; some models extend analysis to T cell infiltration or perform caspase activation assays. However, to our knowledge, T cell motility analysis is not regularly included as an endpoint in imaging studies on cancer spheroids.
Methods: Here, we intend to demonstrate that motility analysis of macrophages and T cells is a valuable functional endpoint for studies on molecular interventions in the tumor microenvironment.
Anti-Tumor Effects of Sheep Umbilical Cord Mesenchymal Stem Cells on Melanoma Cells.
Int J Mol Sci
January 2025
College of Life Science, Northeast Forestry University, Harbin 150040, China.
Melanoma is among the most common malignancies and has recently exhibited increased resistance to treatments, resulting in a more aggressive disease course. Mesenchymal stem cells (MSCs) secrete cytokines both in vivo and in vitro, which regulate tumor cell signaling pathways and the tumor microenvironment, thereby influencing tumor progression. This study investigates the anti-melanogenesis effects of sheep umbilical cord mesenchymal stem cells (SUCMSCs) to assess their potential application in melanoma treatment.
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!