SHROOM3 Antibody
Description
Definition and Molecular Context of SHROOM3 Antibody
SHROOM3 antibodies target the SHROOM3 protein, encoded by the SHROOM3 gene located on human chromosome 4. SHROOM3 regulates actin cytoskeleton organization via Rho kinase (ROCK)-mediated apical constriction and apicobasal elongation in epithelial cells . It is the only SHROOM family member linked to CKD through genome-wide association studies (GWAS), with variants near its transcription start site associated with altered glomerular filtration rate (eGFR) and albuminuria .
Key domains of SHROOM3 include:
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ASD1: Actin-binding domain disrupted by CKD-associated variants (e.g., G1073S) .
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ASD2: Mediates interaction with ROCK1/2 to activate myosin II .
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CC2/CC3: Critical for microtubule regulation and epithelial morphogenesis .
Applications of SHROOM3 Antibodies in Research
SHROOM3 antibodies are widely used in:
Podocyte Integrity and CKD
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SHROOM3 knockdown in mice causes podocyte foot process effacement, albuminuria, and disrupted slit diaphragms due to defective lamellipodia formation .
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Heterozygous Shroom3 mice develop adult-onset glomerulosclerosis and proteinuria, mimicking human CKD progression .
Actin and N-Cadherin Dynamics
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SHROOM3 deficiency reduces apical actin accumulation and disrupts N-cadherin localization in renal tubules, impairing epithelial repair after acute kidney injury (AKI) .
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In Xenopus neural tubes, SHROOM3 loss uncouples actin and N-cadherin dynamics, leading to failed apical constriction .
Therapeutic Implications
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Fullerene-based siRNA delivery targeting Shroom3 in podocytes shows potential for treating nephrotic syndrome .
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SHROOM3 overexpression activates AMPK, reducing protein synthesis and podocyte loss despite smaller glomerular volume .
Validation and Challenges
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Specificity: SHROOM3 antibodies show no cross-reactivity with other SHROOM family proteins (e.g., SHROOM1/2/4) .
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Limitations: Observed molecular weight discrepancies (~68 kDa vs. predicted 216 kDa) suggest isoform-specific detection or post-translational modifications .
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Critical Controls: Co-IP experiments confirm SHROOM3-ROCK1 interaction and actin-binding defects in CKD-linked variants (e.g., G1073S) .
Future Directions
Product Specs
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Target Background
- Two independent cases of protein-truncating de novo mutations in SHROOM3 have been strongly linked to severe human neural tube defects. PMID: 25805808
- Variants disrupting the actin-binding domain of SHROOM3 can lead to podocyte effacement and impairment of the glomerular filtration barrier. PMID: 25273069
- The SNP rs17319721 acts as a cis-acting expression quantitative trait locus of SHROOM3, facilitating TGF-B1 signaling and contributing to allograft injury. PMID: 25437874
- Research indicates that rs1260326 in GCKR (beta=1.30, P = 3.23E-03), rs17319721 in SHROOM3 (beta = -1.28, P-value = 3.18E-03) and rs12917707 in UMOD (beta = 2.0, P-value = 8.84E-04) are significantly associated with baseline estimated GFR. PMID: 23586973
- A recessive missense mutation in SHROOM3 has been associated with heterotaxy syndrome. PMID: 21936905
