CHMP1A Antibody

Definition and Basic Properties of CHMP1A Antibody

CHMP1A Antibody is a polyclonal immunoglobulin G (IgG) antibody raised against the chromatin-modifying protein 1A (CHMP1A), a key component of the ESCRT-III complex and a regulator of chromatin structure. It is primarily used to detect endogenous CHMP1A protein levels in human samples via techniques such as Western blot, immunocytochemistry/immunofluorescence (ICC/IF), and immunohistochemistry (IHC-P) .

Cytoplasmic Functions

• ESCRT-III Complex: Participates in multivesicular body (MVB) formation, enabling degradation of membrane proteins and cytokinesis .

• Vesicular Secretion: Critical for sonic hedgehog (SHH) secretion via extracellular vesicles (EVs), particularly ART-EVs (AXL, RAB18, TMED10) .

Nuclear Functions

• Chromatin Regulation: Recruits Polycomb group proteins (e.g., BMI1/PCGF4) to condensed chromatin, silencing genes like INK4A to promote cell cycle progression .

Clinical and Developmental Relevance

• Microcephaly and Brain Development:

  • CHMP1A mutations cause pontocerebellar hypoplasia and microcephaly due to impaired SHH secretion and neuroprogenitor proliferation .

  • In Chmp1a-null mice, cerebrospinal fluid (CSF) SHH levels are reduced, disrupting forebrain and hindbrain development .

• Kidney Disease:

  • Chmp1a deficiency exacerbates tubulointerstitial fibrosis in cisplatin-induced nephrotoxicity, linked to dysregulated iron trafficking and ferroptosis .

Mechanistic Insights

• SHH Secretion:

  • CHMP1A-dependent ART-EVs are enriched in SHH, AXL, RAB18, and TMED10, ensuring proper signaling in neuroprogenitors .

  • Loss of CHMP1A disrupts MVB formation, reducing SHH release and downstream signaling .

• BMI1-INK4A Axis:

  • CHMP1A recruits BMI1 to INK4A promoters, repressing its expression. Mutations lead to INK4A upregulation, limiting stem cell proliferation .

Antibody Performance

Experimental Data

• Western Blot:

  • Detects a ~22 kDa band in transfected 293T lysates (PCOLN3 transfected vs. non-transfected controls) .

  • Abcam’s ab167412 shows consistent banding in HeLa, LNCaP, and RAW264.7 lysates .

• Immunofluorescence:

  • Localizes CHMP1A to perinuclear regions in HeLa cells, colocalizing with endosomal markers (e.g., RAB7) .

Challenges and Limitations

• Specificity Concerns:

  • Requires controls (e.g., GST-tagged recombinant protein) to exclude cross-reactivity with non-specific epitopes .

• Lot Variability:

  • Concentrations vary between lots; precise titration is essential .

Future Directions

• Therapeutic Targeting: Exploiting CHMP1A’s role in SHH secretion or ferroptosis for neurodegenerative or kidney disease therapies .

• Advanced Antibody Engineering: Development of monoclonal antibodies with improved specificity for subcellular localization studies.