Recombinant Danio rerio Vacuolar ATPase assembly integral membrane protein VMA21 (vma21)
Description
Overview of Recombinant Danio rerio Vacuolar ATPase Assembly Integral Membrane Protein VMA21 (vma21)
Recombinant Danio rerio vacuolar ATPase assembly integral membrane protein VMA21 (vma21) is a bioengineered protein derived from zebrafish, designed to study the assembly and function of the vacuolar ATPase (V-ATPase) complex. This protein is critical for lysosomal acidification, autophagy regulation, and cellular homeostasis. The recombinant form is His-tagged, expressed in E. coli, and spans amino acids 1–104, corresponding to the full-length native protein (UniProt: B8JLV7) .
Domain Architecture
VMA21 is an integral membrane protein with two transmembrane domains and a luminal loop. It interacts with V-ATPase subunits (e.g., ATP6V0C) to facilitate the assembly of the V₀ domain, a process essential for proton translocation into lysosomes . The recombinant zebrafish version retains these structural features, enabling functional studies in heterologous systems.
| Feature | Description | Source |
|---|---|---|
| Protein Length | 104 amino acids (1–104) | |
| Expression System | E. coli | |
| Tag | N-terminal His tag | |
| Function | Chaperones V₀ domain assembly; escorts V₀ to the Golgi for V1 domain binding |
Role in Disease Modeling
Mutations in vma21 cause X-linked myopathy with excessive autophagy (XMEA), characterized by lysosomal dysfunction and autophagic vacuoles. A zebrafish model (vma21 mutants) recapitulates XMEA phenotypes, including impaired lysosomal acidification, reduced Lamp1 staining, and autophagic flux disruption . The recombinant protein may aid in studying these mechanisms or testing therapeutic interventions.
Mechanistic Insights
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Lysosomal Acidification: VMA21 deficiency leads to neutral lysosomes, as shown by LysoTracker Red staining failure in vma21 mutants .
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Autophagy Dysregulation: Mutant zebrafish exhibit increased LC3-II levels and autophagic vacuoles, indicative of stunted autophagic flux .
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Hepatic Pathology: vma21 mutants develop lipid deposition and reduced liver size, mimicking human hepatic steatosis linked to VMA21 defects .
Table 1: Key Experimental Observations in Zebrafish Models
Table 2: Functional Interactions of VMA21
| Interaction Partner | Role in V-ATPase Assembly | Source |
|---|---|---|
| ATP6V0C | Subunit of the V₀ domain; binds VMA21 during proteolipid ring formation | |
| ATP6AP2 | ER chaperone; interacts with VMA21 to mediate V₀ assembly |
Therapeutic Implications
In zebrafish models, compounds like edaravone (antioxidant) and LY294002 (PI3K inhibitor) improved motor function and survival, suggesting potential therapeutic targets for XMEA . The recombinant protein could facilitate high-throughput screening for small-molecule modulators of VMA21 activity.
Product Specs
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Target Background
Essential for the assembly of the V0 complex of the vacuolar ATPase (V-ATPase) within the endoplasmic reticulum.
