RAB18 Human
Description
Vesicle Trafficking and Autophagy
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Regulates vesicle transport between ER, Golgi, and lipid droplets (LDs) .
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Facilitates autophagy by promoting lysosomal degradation of cellular debris .
Lipid Droplet Dynamics
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LD growth: Tethers ER to LDs via the Rab18-NRZ-SNARE complex, enabling lipid transfer for LD expansion .
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Lipid metabolism: Modulates triacylglycerol (TAG) synthesis and storage .
Table 2: Impact of Rab18 Depletion on Lipid Droplets
| Parameter | Wild-Type Cells | Rab18-Deficient Cells |
|---|---|---|
| Mature LDs per cell | 938 ± 105 | 117 ± 13 |
| Supersized LDs (>2 µm) | Rare | Increased 8-fold |
| TAG synthesis rate | Normal | Reduced by 40% |
ER Organization
Cell Migration and Focal Adhesion Dynamics
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Promotes directional cell migration by regulating ER transport to focal adhesions (FAs) .
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Silencing Rab18 reduces FA assembly rate by 2.4-fold and increases disassembly rate by 3-fold .
Warburg Micro Syndrome
Table 3: Reported RAB18 Mutations in Warburg Micro Syndrome
| Mutation Type | Clinical Phenotype | References |
|---|---|---|
| c.565C>T (p.Arg189*) | Early-onset cataracts, microcephaly | |
| c.2T>C (p.Met1?) | Severe motor delay, cortical blindness |
Metabolic Disorders
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Obesity: Rab18 mRNA levels correlate with adiposity in humans, particularly in omental adipose tissue .
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Insulin resistance: Rab18 mediates insulin-stimulated lipogenesis in adipocytes .
Sex- and Depot-Specific Expression
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Adipose tissue: Higher Rab18 expression in subcutaneous vs. omental fat in obese males .
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Sex differences: Females exhibit higher baseline Rab18 levels in omental fat .
Table 4: Rab18 mRNA Levels in Human Adipose Tissue
| Group | Subcutaneous (copies/ng RNA) | Omental (copies/ng RNA) |
|---|---|---|
| Lean males | 2.1 × 10³ | 1.5 × 10³ |
| Obese males (BMI >48) | 4.8 × 10³ | 3.2 × 10³ |
| Lean females | 3.0 × 10³ | 2.7 × 10³ |
Future Directions
Product Specs
Product Science Overview
RAB18 is a gene that encodes a protein belonging to the Rab family of small GTPases. These proteins are key regulators of intracellular membrane trafficking, which includes the formation, movement, and fusion of transport vesicles within cells . The RAB18 protein is involved in various cellular processes, including vesicle trafficking, lipid droplet formation, and maintaining endoplasmic reticulum structure .
The RAB18 gene is located on chromosome 10 in humans . It produces a protein that is ubiquitously expressed, with particularly high expression levels in the brain . The protein encoded by RAB18 cycles between an inactive GDP-bound form and an active GTP-bound form, which allows it to recruit different sets of downstream effectors responsible for vesicle formation, movement, tethering, and fusion .
RAB18 plays a crucial role in several cellular functions:
- Vesicle Trafficking: RAB18 regulates the movement of proteins and other molecules within cells by controlling vesicle trafficking .
- Lipid Droplet Formation: It is required for the localization of ZFYVE1 to lipid droplets and mediates the formation of endoplasmic reticulum-lipid droplets (ER-LD) contacts .
- Endoplasmic Reticulum Structure: RAB18 is essential for maintaining the structure of the endoplasmic reticulum .
- Eye and Brain Development: It plays a key role in the development of the eye and brain, and its dysfunction is associated with neurodegeneration .
