ruffle assembly

Definition

Target type: biologicalprocess

The aggregation, arrangement and bonding together of a set of components to form a ruffle, a projection at the leading edge of a crawling cell; the protrusions are supported by a microfilament meshwork. The formation of ruffles (also called membrane ruffling) is thought to be controlled by a group of enzymes known as Rho GTPases, specifically RhoA, Rac1 and cdc42. [GOC:yaf, http:en.wikipedia.org/wiki/Membrane_ruffling, PMID:12556481]

Ruffle assembly is a dynamic process that involves the rapid and localized reorganization of the actin cytoskeleton at the leading edge of migrating cells. It is driven by a complex interplay of signaling pathways, cytoskeletal proteins, and membrane components. Here's a detailed breakdown of the key steps involved:

**1. Initiation and Signaling:**
- The process often begins with external cues, such as chemoattractants, growth factors, or ECM components, that bind to cell surface receptors.
- This triggers intracellular signaling cascades, involving proteins like Rho GTPases (e.g., Rac1), PI3 kinase, and downstream effectors, leading to local activation of actin polymerization.

**2. Actin Polymerization and Nucleation:**
- Rac1 activation promotes the formation of branched actin networks, driven by the Arp2/3 complex.
- This complex nucleates new actin filaments, providing the building blocks for ruffles.
- Actin-binding proteins, including profilin, cofilin, and capping proteins, regulate the dynamics of filament assembly and disassembly.

**3. Membrane Protrusion and Ruffling:**
- Actin polymerization generates force, pushing the plasma membrane outward, leading to the formation of ruffles.
- These membrane protrusions can be sheet-like, finger-like, or lamellipodia, depending on the specific regulatory mechanisms.

**4. Membrane Recycling and Endocytosis:**
- As ruffles extend, membrane components are recruited to the leading edge, including lipids, proteins, and receptors.
- This process is tightly coupled to endocytosis, which recycles membrane material and regulates the overall size and shape of ruffles.

**5. Adhesion and Traction:**
- Adhesive molecules, such as integrins, attach the ruffles to the underlying substrate, providing traction for cell migration.
- The force generated by actin polymerization is essential for generating the traction needed for cell movement.

**6. Retraction and Deactivation:**
- Ruffles are transient structures, and their assembly and disassembly are dynamically regulated.
- After a period of extension, ruffles can retract, often through the action of myosin II, which contracts the actin filaments.
- Signaling pathways are downregulated, and the process of ruffle assembly is reversed.

**7. Regulation and Feedback Loops:**
- The entire process of ruffle assembly is tightly regulated by complex feedback mechanisms.
- For example, the formation of new ruffles can be modulated by the density and distribution of existing ruffles, ensuring efficient migration and exploration of the surrounding environment.

**In summary, ruffle assembly is a highly orchestrated and dynamic process driven by a complex interplay of signaling pathways, cytoskeletal proteins, and membrane components. This process is crucial for cell motility, migration, and exploration of the surrounding environment.**'
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Proteins (3)

Compounds (94)