RAB10 Human
Description
Biological Functions
RAB10 orchestrates diverse cellular processes through its roles in:
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Endosomal trafficking: Facilitates retrograde transport of TrkB receptors in neurons and TLR4 recycling in macrophages .
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Recycling pathways: Cooperates with Rab22a to form tubular recycling endosomes (TREs) for clathrin-independent cargo .
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Lipid droplet regulation: Promotes autophagic degradation of lipid droplets via EHBP1-EHD2 complexes .
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Membrane repair: Mediates lysosomal exocytosis through interactions with Rab3A .
Alzheimer’s Disease (AD)
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Elevated RAB10 expression correlates with amyloid pathology, suggesting therapeutic targeting could modulate Aβ production .
Breast Cancer
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Overexpression linked to HER2-positive tumors and poor prognosis .
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Drives proliferation, migration, and invasion via AMPK signaling and autophagy .
Inflammatory Disorders
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Enhances TLR4 surface expression, exacerbating LPS-induced lung injury in murine ARDS models .
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Rab10-overexpressing macrophages increase neutrophil infiltration by 20-fold .
Retrograde Axonal Transport
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Rab10 knockdown reduces TrkB accumulation in hippocampal neuron somata by 40%, impairing BDNF-induced CREB phosphorylation .
Endosomal PI(4,5)P2 Regulation
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Rab10 deficiency increases PI(4,5)P2 levels by 2.5×, disrupting membrane fission via ARF-6/CNT-1 pathways .
Therapeutic Targeting
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In vivo studies show Rab10 inhibition reduces Aβ42 toxicity in AD models .
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GTPase-inactive mutants (T23N/Q68L) block TLR4 signaling, suggesting pharmacologic potential .
Comparative Roles in Cellular Pathways
Product Specs
Q&A
What is the fundamental role of RAB10 in cellular processes?
RAB10 regulates vesicle trafficking, membrane dynamics, and intracellular signaling through its GTPase activity. Key functions include:
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Vesicle transport: Mediates exocytosis and endocytosis by coordinating Rab effector proteins .
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Cell proliferation and migration: In breast cancer (BC), RAB10 promotes tumor cell invasion via HER2-associated pathways .
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Synaptic transmission: Modulates neurotransmitter receptor trafficking (e.g., GABA<sub>B</sub>R) in neuronal circuits .
Methodological Insight: To study these roles, use CRISPR/Cas9 knockdown in cell lines (e.g., MDA-MB-231 for BC) combined with transwell migration assays or pHluorin-based synaptic vesicle tracking .
How is RAB10 expression associated with human diseases?
RAB10 dysregulation is implicated in:
Experimental Design: Validate associations using immunohistochemistry on patient tissue microarrays (BC cohorts) or RNA-seq on postmortem brain samples (neurodegeneration studies) .
What are standard methods to detect RAB10 activity in human samples?
Best Practice: Combine orthogonal methods (e.g., IHC + RNAscope) to control for antibody specificity.
How to resolve contradictory findings on RAB10’s role in cognitive functions?
The neurobehavioral paradox in Rab10<sup>+/−</sup> mice illustrates this challenge:
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Improved performance: Object-in-place memory (hippocampal-dependent) .
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Impaired performance: Trace eyeblink conditioning (cortico-hippocampal circuits) .
Resolution Strategy:
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Circuit-specific analysis: Use region-specific KO models (e.g., AAV-Cre in dorsal hippocampus vs. prefrontal cortex).
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Single-cell RNA-seq: Identify differential gene networks (e.g., upregulated Grin2d in cortex vs. downregulated Vegfa in hippocampus) .
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Behavioral phenotyping: Employ complementary tasks (Morris water maze, TECC) to disentangle cognitive domains .
What experimental models best capture RAB10’s disease-relevant functions?
| Model | Strengths | Limitations |
|---|---|---|
| BC cell lines (MCF-7) | High-throughput drug screening | Lack tumor microenvironment |
| Rab10<sup>+/−</sup> mice | Study haploinsufficiency effects | Developmental compensation |
| Cocaine self-administration (rats) | Addiction-relevant circuits | Limited translational validity |
Design Tip: For addiction studies, pair Rab10 knockdown in nucleus accumbens with in vivo fiber photometry to track GABA<sub>B</sub>R dynamics during cocaine exposure .
What mechanistic insights explain RAB10’s dual roles in cancer and neurodegeneration?
Hypothesis: Tissue-specific interaction networks determine functional outcomes.
| Context | Key Interactors | Downstream Effect |
|---|---|---|
| Breast cancer | HER2, MMP9 | ↑ Metastasis via ECM remodeling |
| Neurons | GRIN2D, GABA<sub>B</sub>R | Altered NMDA receptor signaling |
Validation Workflow:
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Co-IP/mass spectrometry to identify context-dependent binding partners.
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Spatial transcriptomics to map interaction hubs in BC vs. brain tissues.
How to integrate multi-omics data for RAB10 pathway analysis?
A study on Rab10<sup>+/−</sup> mice demonstrated this approach:
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Transcriptomics: 16 DEGs identified (e.g., Prkaa2↑, Vegfa↓).
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Pathway enrichment: Neuroinflammation (↓), synaptic plasticity (↑).
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Behavioral correlation: Grin2d upregulation linked to spatial memory enhancement.
Toolkit:
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STRING DB: Map protein-protein interactions.
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GSEA: Rank pathways by enrichment score (FDR < 0.25).
How to address variability in RAB10 antibody performance?
Issue: Commercial antibodies show batch-dependent specificity .
Solutions:
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Validation triad:
What statistical approaches are optimal for RAB10 clinical correlations?
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Cox regression: HR = 1.8 (95% CI: 1.2–2.5) for RAB10<sup>high</sup> vs. low.
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Kaplan-Meier analysis: Stratified by HER2 status (log-rank p < 0.01).
Advanced Tip: For small cohorts (n < 50), apply bootstrapping (1,000 iterations) to estimate confidence intervals.
Table 1. RAB10-Associated Genes in Disease Models
| Gene | Regulation | Function | Disease Context | Source |
|---|---|---|---|---|
| HER2 | ↑ | RAB10 co-amplification | Breast cancer | |
| Grin2d | ↑ | NMDA receptor subunit | Neurodegeneration | |
| GABA<sub>B</sub>R | ↓ | Receptor internalization | Addiction |
Table 2. Behavioral Outcomes in Rab10<sup>+/−</sup> Mice
| Test | Performance vs. WT | Neural Circuit Involved |
|---|---|---|
| Object-in-place | ↑ 25% preference ratio | Hippocampus-perirhinal cortex |
| Trace eyeblink | ↓ 40% CR amplitude | Cortico-hippocampal |
| Cocaine locomotion | ↓ 50% distance traveled | Nucleus accumbens GABA<sub>B</sub>R |
Product Science Overview
RAB10 cycles between an inactive GDP-bound form and an active GTP-bound form. In its active form, it recruits various downstream effectors responsible for vesicle formation, movement, tethering, and fusion . This protein is involved in several critical cellular processes, including:
- Endocytic Recycling: RAB10 is a key regulator of endocytic recycling, especially in the basolateral recycling pathways of polarized epithelial cells . It is required for the recruitment of CNT-1 to endosomal membranes in the intestinal epithelium .
- Protein Transport: It regulates the transport of the SLC2A4/GLUT4 glucose transporter-enriched vesicles to the plasma membrane . Additionally, it is involved in the transport of TLR4, a toll-like receptor, to the plasma membrane, which is important for the innate immune response .
- Neuronal Development: In neurons, RAB10 is involved in axonogenesis through the regulation of vesicular membrane trafficking toward the axonal plasma membrane .
Mutations or dysregulation of RAB10 have been associated with various diseases. For instance, it has been linked to Charcot-Marie-Tooth Disease, Recessive Intermediate B, and Astrocytoma, IDH-Mutant, Grade 2 . Understanding the function and regulation of RAB10 can provide insights into these diseases and potentially lead to the development of targeted therapies.
Recombinant human RAB10 protein is often used in research to study its function and role in various cellular processes. This recombinant protein is typically expressed in E. coli and purified for use in various assays . It is a valuable tool for scientists studying intracellular trafficking, protein transport, and related cellular mechanisms.
