Related Experiment Video
Updated: Aug 13, 2025
10:43
Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration
Published on: May 19, 2016
6.8K
ArpC5 isoforms regulate Arp2/3 complex-dependent protrusion through differential Ena/VASP positioning
Florian Fäßler1, Manjunath G Javoor1, Julia Datler1
1Institute of Science and Technology Austria (ISTA), Klosterneuburg, Austria.
Science Advances
|January 20, 2023
Summary
The Arp2/3 complex subunit isoforms ArpC5 and ArpC5L differentially regulate cell migration by affecting actin network stability and dynamics. These isoforms influence Ena/VASP protein positioning, suggesting a signaling pathway that enhances cell movement.
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- Actin networks are crucial for cell migration, with the Arp2/3 complex mediating branched actin nucleation.
- Subunit isoforms of the Arp2/3 complex, such as ArpC5 and ArpC5L, are emerging regulators of its activity.
- Understanding isoform-specific roles is key to deciphering Arp2/3 complex function in cellular processes.
Purpose of the Study:
- To investigate the differential effects of ArpC5 and ArpC5L isoforms on cell migration.
- To elucidate the structural and dynamic mechanisms by which these isoforms influence actin networks.
- To explore the interplay between ArpC5 isoforms and Ena/VASP proteins in regulating actin assembly.
Main Methods:
- Reverse genetics approaches were employed to study ArpC5 and ArpC5L.
- Cellular structural biology techniques were utilized to analyze actin network ultrastructure.
- Protein dynamics and positioning of Ena/VASP family members were assessed.
Main Results:
- ArpC5 and ArpC5L isoforms differentially impact cell migration dynamics.
- Both isoforms stabilize ArpC1 at branch junctions, influencing protrusion characteristics and actin network ultrastructure.
- ArpC5 isoforms dictate the positioning of Ena/VASP proteins, modulating actin assembly levels.
Conclusions:
- ArpC5 and ArpC5L play distinct roles in regulating Arp2/3 complex-mediated cell migration.
- The ArpC5-Ena/VASP axis represents a novel signaling pathway that enhances cell migration.
- Differential subunit composition provides a mechanism for fine-tuning actin network formation and cell motility.
Related Concept Videos
01:14Generation of Straight or Branched Actin Filaments
3.0K
The straight or branched structure formation of actin filaments is controlled by nucleating proteins such as the formins and Arp2/3 complex. Formin-mediated assembly results in straight filaments, whereas Arp2/3 protein complex-mediated assembly results in branched actin filaments.
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
3.0K
01:31Mechanism of Lamellipodia Formation
2.7K
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...
2.7K
01:39Mechanism of Filopodia Formation
2.4K
Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
2.4K
01:33Coat Assembly and GTPases
3.6K
Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
3.6K
01:14Rab Proteins
4.0K
Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
4.0K
01:34Directing Proteins to the Rough Endoplasmic Reticulum
7.3K
The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
7.3K