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regulation of Arp2/3 complex-mediated actin nucleation

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of actin nucleation mediated by the Arp2/3 complex and interacting proteins. [GOC:mah]

The Arp2/3 complex is a protein complex that plays a crucial role in the regulation of actin nucleation, a key process in cell motility, endocytosis, and other cellular functions. Actin nucleation refers to the formation of new actin filaments, which are essential for generating the force required for these processes. The Arp2/3 complex acts as a nucleation-promoting factor (NPF), promoting the assembly of new actin filaments from pre-existing ones. This process is tightly regulated by a variety of signaling pathways and cellular factors, ensuring that actin polymerization occurs in the right place and at the right time.

Here is a detailed description of the biological process of regulation of Arp2/3 complex-mediated actin nucleation:

**1. Activation of the Arp2/3 Complex:**
* **Nucleation-Promoting Factors (NPFs):** The Arp2/3 complex is inactive in its resting state. To become active, it needs to be activated by NPFs, which bind to the complex and induce conformational changes that allow it to initiate actin filament formation. Key NPFs include:
* **WASP Family Proteins (Wiskott-Aldrich Syndrome Protein):** These proteins are activated by a variety of stimuli, including cell surface receptors and Rho GTPases. They bind to the Arp2/3 complex and promote its activation.
* **SCAR/WAVE Family Proteins:** Similar to WASP family proteins, SCAR/WAVE proteins are activated by signaling pathways and interact with the Arp2/3 complex to promote actin nucleation.

**2. Actin Filament Assembly:**
* **Nucleation Site Formation:** The activated Arp2/3 complex binds to the side of an existing actin filament (the "mother" filament). This binding event creates a new nucleation site where new actin monomers can assemble.
* **Actin Monomer Addition:** The Arp2/3 complex recruits actin monomers to the nucleation site. The complex acts as a template, providing a favorable environment for the assembly of new actin filaments.
* **Branch Formation:** The newly formed filament (the "daughter" filament) branches off from the mother filament at a 70-degree angle, creating a characteristic branched actin network.

**3. Regulation of Actin Nucleation:**
* **Signal Transduction:** Actin nucleation is tightly regulated by various signal transduction pathways, ensuring that it occurs only when and where it is needed. These pathways involve a range of molecules, including:
* **Rho GTPases:** These small GTPases are involved in regulating cell shape, motility, and cytoskeletal organization. They activate NPFs, such as WASP and SCAR/WAVE proteins, which in turn activate the Arp2/3 complex.
* **Cellular Factors:** Several cellular factors influence the activity of the Arp2/3 complex and actin nucleation, including:
* **Phosphoinositides:** These lipid signaling molecules regulate the localization and activity of NPFs and the Arp2/3 complex.
* **Actin-Binding Proteins:** Proteins that bind to actin filaments can regulate their assembly and disassembly, thereby influencing the activity of the Arp2/3 complex.
* **Other Regulatory Proteins:** A number of other proteins interact with the Arp2/3 complex and its associated proteins, modulating its activity and function.

**4. Role in Cellular Processes:**
* **Cell Motility:** The Arp2/3 complex is crucial for the formation of the lamellipodia and filopodia, which are protrusions that allow cells to move. The branched actin networks generated by the Arp2/3 complex provide the force needed for these protrusions to extend.
* **Endocytosis:** The Arp2/3 complex is involved in the formation of the clathrin-coated pits that are responsible for the internalization of molecules and particles into the cell.
* **Other Processes:** The Arp2/3 complex is also involved in a variety of other cellular processes, including:
* **Vesicle trafficking:** Transporting cargo within the cell.
* **Cell division:** During cytokinesis, the Arp2/3 complex helps to constrict the cell membrane, dividing the cell into two daughter cells.
* **Organelle positioning:** Maintaining the organization of intracellular structures.

**Overall, the regulation of Arp2/3 complex-mediated actin nucleation is a complex and highly coordinated process that involves a multitude of signaling pathways and cellular factors. This intricate control ensures that actin polymerization occurs in a precise and regulated manner, contributing to a wide range of essential cellular functions.**'
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Proteins (1)

ProteinDefinitionTaxonomy
ADP-ribosylation factor 1An ADP-ribosylation factor 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P84077]Homo sapiens (human)

Compounds (1)

CompoundDefinitionClassesRoles
(2S)-2-[[2-(2,3-dihydro-1H-inden-5-yloxy)-9-[(4-phenylphenyl)methyl]-6-purinyl]amino]-3-phenyl-1-propanolbiphenyls