Related Experiment Video
Updated: Jun 8, 2026
14:23
Quantitative Measurement of Invadopodia-mediated Extracellular Matrix Proteolysis in Single and Multicellular Contexts
Published on: August 27, 2012
Nck1 and Grb2 localization patterns can distinguish invadopodia from podosomes
Matthew Oser1, Athanassios Dovas, Dianne Cox
1Department of Anatomy and Structural Biology, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461, USA. matthew.oser@med.einstein.yu.edu
European Journal of Cell Biology
|September 21, 2010
Summary
Invadopodia and podosomes are cell structures that degrade matrices. This study found distinct protein activators, Nck1 and Grb2, localize to invadopodia versus podosomes, aiding classification of these matrix-degrading structures.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Invadopodia and podosomes are matrix-degrading ventral cell surface structures.
- Both structures are involved in actin polymerization and N-WASp/WASp-dependent Arp2/3-complex activation.
- The specific upstream mediators for N-WASp/WASp activation in invadopodia versus podosomes are not fully understood.
Purpose of the Study:
- To investigate the localization patterns of N-WASp/WASp activators Nck1 and Grb2.
- To determine if invadopodia and podosomes utilize distinct mediators for N-WASp/WASp activation.
- To establish molecular markers for sub-classifying ventral cell surface degradative structures.
Main Methods:
- Immunofluorescence microscopy was used to examine protein localization.
- Localization patterns of Nck1 and Grb2 were analyzed in invadopodia (metastatic mammary carcinoma cells), podosomes (macrophages), and degradative structures (Src-transformed fibroblasts, PMA-stimulated endothelial cells).
Main Results:
- Nck1 specifically localized to invadopodia, but not to podosomes or other degradative structures.
- Grb2 specifically localized to degradative structures in Src-transformed fibroblasts and PMA-stimulated endothelial cells, but not invadopodia or podosomes.
- Distinct upstream activators (Nck1 and Grb2) were identified for invadopodia and podosomes.
Conclusions:
- Invadopodia and podosomes utilize distinct upstream activators for N-WASp/WASp activation.
- Ventral cell surface degradative structures possess distinguishing molecular and structural characteristics.
- Nck1 and Grb2 localization patterns can be used to sub-classify these structures.
Related Concept Videos
01:35Cancer Cell Migration through Invadopodia
Invadosome is a broad category of cell surface structures with proteolytic activity that degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However, invadopodia can...
01:28Types of Membrane Protrusions
The protrusion of the cell surface is an initial step for several cellular processes, including cell migration, phagocytosis, and neurite outgrowth. These membrane protrusions are a result of cytoskeletal rearrangement. The most widely observed cell protrusions include lamellipodia, pseudopodia, filopodia, microvilli, invadopodia, and podosomes. These protrusions can be of two types — static or dynamic.
The microvilli, an example of stable protrusions, are finger-like projections with a...
The microvilli, an example of stable protrusions, are finger-like projections with a...
01:31Mechanism of Lamellipodia Formation
Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
01:21Cell Polarization by Rho Proteins
Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
01:16Cell Motility through Blebbing
Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
Blebbing Through the Matrix
In multicellular...
Blebbing Through the Matrix
In multicellular...
01:32Pinching-off of Coated Vesicles
Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...