regulation of stress fiber assembly

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of the assembly of a stress fiber, a bundle of microfilaments and other proteins found in fibroblasts. [GOC:ai]

Stress fiber assembly is a complex process involving the coordinated action of various proteins and signaling pathways. It is tightly regulated to maintain cell shape, adhesion, and motility. Here's a detailed description:

**1. Signaling Events:**

* **Mechanical cues:** Stretching, pressure, and other physical forces on the cell membrane trigger signaling pathways, leading to the activation of Rho GTPases, particularly RhoA.
* **Chemical signals:** Growth factors, cytokines, and other soluble factors can also stimulate RhoA activity, leading to stress fiber formation.
* **Other pathways:** Integrin-mediated adhesion, cell-cell contact, and various intracellular pathways can also influence stress fiber assembly.

**2. Rho GTPase Activation:**

* Activated RhoA initiates a cascade of downstream signaling events by activating its effector proteins, including Rho-kinase (ROCK) and formin homology proteins (FHNs).

**3. Actin Polymerization and Bundling:**

* **ROCK:** ROCK phosphorylates myosin light chain (MLC), which enhances its ATPase activity and promotes the formation of actomyosin filaments. ROCK also phosphorylates and inactivates myosin phosphatase, preventing the dephosphorylation of MLC and further promoting actomyosin assembly.
* **FHNs:** FHNs, such as Diaphanous-related formins (Dia), act as nucleation-promoting factors, accelerating the assembly of actin filaments.

**4. Stress Fiber Organization and Alignment:**

* **α-actinin:** This protein crosslinks actin filaments into bundles, contributing to the formation of thick stress fibers.
* **Myosin II:** Myosin II motor proteins interact with actin filaments, generating contractile force and aligning the stress fibers along the direction of tension.
* **Other proteins:** Several other proteins, including filamin, calponin, and tropomyosin, play roles in regulating stress fiber assembly and stability.

**5. Feedback Mechanisms:**

* The assembly of stress fibers can influence signaling pathways, creating feedback loops. For example, the tension generated by stress fibers can activate integrins, further promoting the assembly of focal adhesions and stress fiber formation.

**Regulation:**

* **Rho GTPase regulation:** The activity of Rho GTPases is tightly controlled by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), which promote GTP-bound (active) and GDP-bound (inactive) states, respectively.
* **Phosphorylation and dephosphorylation:** Phosphorylation events, mediated by kinases like ROCK and phosphatases, regulate the activity of key proteins involved in stress fiber assembly.
* **Protein interactions:** Interactions between different proteins, such as actomyosin complexes and signaling molecules, modulate the assembly and stability of stress fibers.

**Consequences:**

* The proper regulation of stress fiber assembly is essential for maintaining cell shape, adhesion, and motility.
* Dysregulation of stress fiber assembly can contribute to various pathological conditions, such as cancer cell invasion, fibrosis, and vascular disease.'
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Proteins (8)

Compounds (290)