RND1 Human
Description
Cytoskeletal Regulation
RND1 inhibits actomyosin contractility and stress fiber formation by:
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Activating p190RhoGAP: Enhances RHOA inactivation, reducing cytoskeletal tension .
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Disrupting cortical actin: Induces dendritic cell morphology and reduces focal adhesions .
Oncogenic and Tumor-Suppressive Functions
RND1 exhibits context-dependent roles in cancer:
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Tumor Suppression:
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Therapeutic Modulation:
Table 2: Clinical Correlations of RND1 Expression
Role in Innate Immunity
RND1 protects against pathogens through two distinct mechanisms:
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Viral Defense:
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Bacterial Defense:
Table 3: Immune-Related Functions of RND1
| Pathogen | Mechanism | Outcome | Source |
|---|---|---|---|
| Viruses (e.g., NDV, PR8) | RHOA inhibition → calcium regulation | Reduced viral entry | |
| Bacteria (e.g., Listeria) | Cytokine induction (IL-6, TNF-α) | Enhanced bacterial clearance |
Transcriptional and Post-translational Control
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Inducers: Pro-inflammatory cytokines (e.g., TNF-α, IL-1β) and Notch signaling in endothelial cells .
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Repressors: ROCK1-mediated phosphorylation of p190RhoGAP, which disrupts RND1-RHOA interaction .
Interacting Partners
Therapeutic Potential
RND1’s dual role in cancer suppression and immune modulation positions it as a candidate for targeted therapies:
Product Specs
Q&A
RND1 (Rho family GTPase 1) is a constitutively active small GTPase with multifaceted roles in cellular processes and disease mechanisms. Below are structured FAQs addressing key research considerations, supported by experimental methodologies and data from peer-reviewed studies.
Advanced Research Questions
How to reconcile RND1's contradictory roles in cancer?
RND1 acts as a tumor suppressor in HCC but shows context-dependent roles in glioblastoma (GBM):
What strategies validate RND1-plexin interactions in neural development?
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Co-immunoprecipitation: Co-transfect RND1 and plexin-B1 in COS-7 cells, immunoprecipitate with anti-plexin antibodies ( ).
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Growth cone collapse assays: Treat hippocampal neurons with Sema4D and quantify collapse rates via live imaging ( ).
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RND1 mutants: Use GTPase-deficient RND1 (T55N) to test plexin-B1-dependent RHOA activation ( ).
How to address variability in RND1-driven cytokine production?
In bacterial infections, RND1 upregulates IL-6/TNF-α via NF-κB ( ). Experimental controls include:
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NF-κB reporter assays: Co-transfect RND1 with NF-κB-luciferase constructs in HeLa cells.
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Cytokine blockade: Treat cells with IL-6/TNF-α neutralizing antibodies and measure bacterial load (CFU assays) ( ).
Technical Challenges & Solutions
Why does RND1 exhibit constitutive activity, and how does this impact assays?
Unlike other Rho GTPases, RND1 lacks intrinsic GTPase activity due to substitutions in catalytic residues (e.g., D63V) ( ). Mitigate assay interference by:
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Dominant-negative constructs: Use RND1-S28N to sequester upstream activators.
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Localization studies: Tag RND1 with fluorescent markers (e.g., GFP) to track membrane association.
How to resolve discrepancies in RND1's role in ferroptosis?
In GBM, RND1 enhances ferroptosis via p53-SLC7A11 ( ). Confounders include:
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p53 status: Use isogenic p53 WT/KO cell lines.
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Lipid peroxidation assays: Combine BODIPY 581/591 C11 with RND1 overexpression.
Product Science Overview
The Rho family of GTPases is a subfamily of the Ras superfamily of small (~21 kDa) signaling G proteins. These proteins play a crucial role in regulating various aspects of intracellular actin dynamics, which are essential for cell movement, organelle development, and other cellular functions . The Rho family includes several members, with RhoA, Rac1, and Cdc42 being the most extensively studied .
The identification of the Rho family of GTPases began in the mid-1980s. The first member, RhoA, was isolated in 1985 through a low stringency cDNA screening . Subsequently, Rac1 and Rac2 were identified in 1989, followed by Cdc42 in 1990 . Over the years, additional members were discovered, leading to the identification of 20 mammalian Rho GTPases distributed across eight subfamilies .
Rho GTPases act as molecular switches, cycling between an inactive GDP-bound state and an active GTP-bound state . This switching mechanism allows them to interact with various downstream effectors, thereby regulating multiple cellular processes. The primary functions of Rho GTPases include:
- Cytoskeletal Dynamics: Rho GTPases regulate the organization of the actin cytoskeleton, influencing cell shape, polarity, and movement .
- Cell Division and Proliferation: They play a role in cell cycle progression and mitosis .
- Gene Expression: Rho GTPases are involved in the regulation of gene transcription .
- Cell Adhesion: They modulate cell-cell and cell-matrix adhesion, which are critical for tissue integrity and repair .
The activity of Rho GTPases is tightly regulated by three classes of proteins:
- Guanine Nucleotide Exchange Factors (GEFs): These proteins activate Rho GTPases by facilitating the exchange of GDP for GTP .
- GTPase-Activating Proteins (GAPs): GAPs inactivate Rho GTPases by accelerating the hydrolysis of GTP to GDP .
- Guanine Nucleotide Dissociation Inhibitors (GDIs): GDIs sequester Rho GTPases in the cytoplasm, preventing their activation .
Human recombinant Rho GTPase 1 is a laboratory-produced version of the naturally occurring protein. It is used extensively in research to study the protein’s structure, function, and role in various cellular processes. Recombinant proteins are produced by inserting the gene encoding the protein into an expression system, such as bacteria or yeast, which then synthesizes the protein in large quantities.
Recombinant Rho GTPase 1 is used in various experimental setups to:
- Investigate Signal Transduction Pathways: Understanding how Rho GTPases transmit signals within cells .
- Study Cytoskeletal Dynamics: Exploring the role of Rho GTPases in actin filament organization .
- Examine Disease Mechanisms: Researching the involvement of Rho GTPases in diseases such as cancer and neurodegenerative disorders .
