CYTH3 Human
Description
2.1. Membrane Trafficking and Cellular Signaling
CYTH3 regulates Golgi structure, receptor recycling, and vesicular transport via ARF activation:
-
Insulin signaling: Required for glucose transporter 4 (GLUT4) translocation in adipocytes, linking insulin to glucose uptake .
-
Receptor trafficking: Promotes Met receptor recycling in endothelial cells and β1 integrin trafficking in HeLa cells .
-
Neuronal function: Supports neurite outgrowth and synaptic transmission by activating ARF6 .
2.2. Metabolic Regulation
CYTH3 knockout mice exhibit insulin resistance, reduced lipogenesis, and altered lipid metabolism:
| Parameter | Wild-Type Mice | CYTH3 Knockout Mice |
|---|---|---|
| Blood glucose (CD) | Normal | 11% lower |
| Insulin tolerance | Responsive | Impaired |
| Hepatic GCK/Pepck expression | Normal | Downregulated |
3.1. Neurodegenerative Diseases
CYTH3 interacts with misfolded proteins in amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD):
-
ALS: Facilitates degradation of mutant SOD1 (G85R) via ARF1/5 activation, mitigating ER stress and neurotoxicity .
-
AD: Modulates amyloid-β clearance and synaptic dysfunction, though mechanisms remain under investigation .
3.2. Prostate Smooth Muscle Contraction
CYTH3 regulates α1-adrenergic and neurogenic contractions in the prostate stroma:
| Stimulus | Effect of SecinH3 (CYTH3 Inhibitor) |
|---|---|
| Norepinephrine | Inhibited contraction |
| Endothelin-1 | Reduced force |
| Electrical stimulation | Diminished response |
3.3. Cancer and Metastasis
-
HGF-induced migration: CYTH3 isoforms with di-glycine PH domains drive Met-dependent cell scattering and invasion .
-
Integrin trafficking: Silencing CYTH3 disrupts β1 integrin recycling, impairing cancer cell adhesion and migration .
Tissue Expression and Localization
CYTH3 exhibits cytoplasmic expression across multiple tissues, with notable activity in:
5.1. Inhibitors
-
SecinH3: A pan-cytohesin inhibitor that blocks Sec7 domain activity (IC₅₀ ~10 µM), disrupting ARF activation and cellular processes .
-
siRNA/shRNA: Targeted knockdown of CYTH3 mRNA in cell lines (e.g., HepG2, 3T3-L1) .
5.2. Antibodies
Product Specs
Product Science Overview
Cytohesin 3, also known as CYTH3, ARNO3, or GRP1, is a protein encoded by the CYTH3 gene in humans . This protein is a member of the cytohesin family, which is characterized by a specific structural organization that includes an N-terminal coiled-coil motif, a central Sec7 domain, and a C-terminal pleckstrin homology (PH) domain . These domains are crucial for the protein’s function in cellular processes such as protein sorting and membrane trafficking.
Cytohesin 3 plays a significant role in the regulation of protein sorting and membrane trafficking. It is involved in the control of Golgi structure and function and may regulate ADP-ribosylation factor protein 6 (ARF6) functions, in addition to acting on ARF1 . The protein promotes guanine-nucleotide exchange on ARF1 and ARF6, facilitating the activation of ARF factors through the replacement of GDP with GTP .
Recombinant Human Cytohesin 3 is typically produced in Escherichia coli (E. coli) expression systems. The protein is expressed as a full-length protein, often with a His-tag at the N-terminus to facilitate purification . The purification process involves conventional chromatographic techniques to achieve high purity levels suitable for various applications, including SDS-PAGE .
Recombinant Cytohesin 3 is used in various research applications, particularly in studies related to cellular signaling, protein-protein interactions, and membrane trafficking. Its ability to promote guanine-nucleotide exchange makes it a valuable tool for investigating ARF-mediated signaling pathways .
