AIF1L Human
Description
Functional Domains and Mechanisms
AIF1L primarily regulates cytoskeletal dynamics and cell morphology:
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Actin Bundling: Promotes F-actin stabilization, critical for stress fibers and focal adhesions .
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Actomyosin Contractility: Modulates non-muscle myosin-II (MYH9, MYL9) and chaperones (UNC45A) to control cell shape .
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Nuclear Localization: Interacts with chromatin-regulating proteins, suggesting roles in transcriptional control .
Tissue Expression and Localization
AIF1L exhibits tissue-specific expression distinct from AIF1:
Localization:
Immune Response and Inflammation
AIF1L is implicated in immune cell regulation but differs from AIF1 in tissue specificity:
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Macrophages: Absent in macrophages; expressed in epithelial and endothelial cells .
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Cancer: Downregulated in breast cancer, correlating with increased migration and poor prognosis .
Podocyte Function and Kidney Disease
AIF1L stabilizes podocyte morphology by:
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Reducing Filopodia: Genetic deletion increases filopodial extensions, disrupting glomerular barrier integrity .
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Regulating Contractility: Interacts with MYL9 and UNC45A to maintain actomyosin balance .
Metabolic Regulation
Contrary to AIF1’s role in obesity, AIF1L-deficient mice show:
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No Impact on Obesity: Similar weight gain, fat mass, and glucose handling under high-fat diet (HFD) .
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Circadian Activity: Reduced physical activity in HFD-fed mice, suggesting potential roles in circadian rhythms .
Table 2: Key Research Findings
Therapeutic Potential and Future Directions
AIF1L’s role in cancer and kidney disease highlights its potential as a therapeutic target:
Product Specs
Q&A
AIF1L (Allograft Inflammatory Factor 1-Like) is an actin-bundling protein with emerging roles in cellular dynamics and disease pathogenesis. Below are structured FAQs for researchers investigating its functions and mechanisms in human systems, organized by research complexity and methodological approaches.
What molecular techniques confirm AIF1L's interaction with actomyosin components?
Methodological Answer:
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SILAC-based proteomics combined with immunoprecipitation reliably identifies AIF1L interactors. In podocytes, this approach revealed MYL9 (myosin regulatory light chain) and UNC45A (myosin chaperone) as top interactors .
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Validation: Co-IP/Western blotting with knockout controls (e.g., AIF1L-KO podocytes) reduces false positives .
| Key Interactors | Functional Role | Localization |
|---|---|---|
| MYL9 | Actomyosin regulation | Stress fibers |
| UNC45A | Myosin folding | Cytoplasm |
| ERM proteins | Membrane-cytoskeleton linkage | Cell cortex |
How does AIF1L influence cellular morphology?
Experimental Design:
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CRISPR-Cas9 knockout models in immortalized podocytes show increased filopodia formation (stained with phalloidin) and reduced actomyosin contractility (via traction force microscopy) .
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Functional rescue: Transfection with WT AIF1L restores baseline contractility .
How to resolve contradictions in AIF1L's role across cancer vs. metabolic studies?
Data Contradiction Analysis:
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Cancer context: AIF1L promotes breast cancer proliferation via cyclin D1 upregulation .
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Metabolic studies: AIF1L-KO mice show no differences in diet-induced obesity or glucose handling .
Methodological Considerations: -
Tissue specificity: AIF1L is absent in liver/spleen but enriched in kidney/adipose . Use tissue-specific knockout models (e.g., Podocin-Cre for podocytes).
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Cell-type profiling: Single-cell RNA sequencing distinguishes AIF1L expression in adipocytes vs. macrophages .
What advanced imaging techniques localize AIF1L's nuclear vs. cytoskeletal roles?
Multi-modal Imaging Workflow:
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Structured illumination microscopy (SIM) resolves AIF1L at filopodial bases and stress fibers .
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Subcellular fractionation + Western blotting confirms nuclear AIF1L (validated by Lamin B1) .
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Live-cell imaging: GFP-tagged AIF1L tracks real-time dynamics during protrusion formation .
How do AIF1L and AIF1 differ mechanistically despite structural homology?
Functional Divergence Table:
| Feature | AIF1L | AIF1 |
|---|---|---|
| Tissue Expression | Kidney, adipose, brain | Spleen, macrophages |
| Metabolic Role | No HFD-linked phenotype | Linked to obesity/diabetes |
| Disease Association | Breast cancer | Rheumatoid arthritis |
Methodological Insight:
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Phylogenetic analysis: EF-hand domain alignment reveals conserved actin-binding regions but divergent N-terminal sequences .
What in vivo models best recapitulate AIF1L's human pathophysiology?
Model Selection Criteria:
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Podocyte injury models: Adriamycin-induced nephropathy in AIF1L-KO mice to assess foot process effacement .
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Xenograft tumors: Breast cancer cell lines with AIF1L knockdown (shRNA) implanted in NSG mice .
Key Parameters:
Product Science Overview
Allograft Inflammatory Factor 1 Like (AIF1L) is a protein encoded by the AIF1L gene in humans. This protein is part of the allograft inflammatory factor family and is known for its role in actin binding and bundling. AIF1L is an actin-binding protein that promotes actin bundling and is involved in various cellular processes, including cytoskeletal organization and cell motility .
AIF1L is expressed in various tissues, with a biased expression in the kidney, spleen, and several other tissues . The protein is primarily localized in the cytoplasm and is associated with the actin cytoskeleton. It is also found in the plasma membrane, cell projections, and extracellular exosomes .
AIF1L is an actin-binding protein that promotes actin bundling, which is essential for maintaining the structural integrity of the cytoskeleton. Unlike other members of the allograft inflammatory factor family, AIF1L does not bind calcium and does not depend on calcium for its function . The protein plays a crucial role in various cellular processes, including actin filament bundle assembly and ruffle assembly .
AIF1L is involved in several biological processes, including cytoskeletal organization, cell motility, and intracellular signaling. The protein’s ability to bind and bundle actin filaments is critical for maintaining the structural integrity of the cytoskeleton and facilitating cellular movements . Additionally, AIF1L is implicated in various physiological and pathological conditions, including inflammation and immune responses .
Research has shown that AIF1L is associated with several inflammatory diseases and conditions. The protein’s role in actin bundling and cytoskeletal organization makes it a potential target for therapeutic interventions in diseases characterized by cytoskeletal abnormalities and inflammation . Further studies are needed to fully understand the clinical implications of AIF1L and its potential as a therapeutic target.
