CLC2 Antibody

Molecular Target: ClC-2 Chloride Channel

ClC-2 is a member of the CLC family of chloride channels, characterized by:

• Structure: Homodimeric architecture with two pores, each formed by a subunit containing 18 α-helical transmembrane domains .

• Function: Activated by hyperpolarization, cell swelling, and extracellular acidification. Facilitates Cl⁻ efflux to regulate membrane potential and intracellular Cl⁻ concentration .

• Localization:

  • Basolateral membranes of intestinal and renal epithelial cells (absorptive role) .

  • Apical regions of ciliated airway epithelial cells and type II pneumocytes .

  • Brain astrocytes and oligodendrocytes, where disruptions cause leukodystrophy .

Antibody Characteristics

CLC2 antibodies are typically raised against epitopes in the intracellular C-terminal domain. Key examples include:

Key Validations:

• KO Validation: Anti-CLC-2 (#ACL-002) shows absence of signal in ClC-2 knockout mice, confirming specificity .

• Western Blot: Detects ~97–99 kDa bands in brain, kidney, and epithelial lysates .

• Subcellular Localization: Co-localizes with H⁺/K⁺-ATPase in gastric parietal cells and occludin in tight junctions .

Role in Epithelial Function

• Intestinal Absorption: ClC-2 localizes to basolateral membranes of duodenal and colonic epithelial cells, supporting Cl⁻ absorption .

  • Mutating the di-leucine motif (L812L813) in its C-terminus redirects ClC-2 to apical membranes, altering epithelial polarity .

• Airway Epithelium: Apical ClC-2 in ciliated cells may compensate for CFTR dysfunction in cystic fibrosis .

Neurological and Reproductive Pathology

• Leukodystrophy: Clcn2 knockout mice develop vacuolar brain degeneration, primarily due to disrupted Cl⁻ homeostasis in astrocytes and oligodendrocytes .

• Testicular Degeneration: Germ cell-specific Clcn2 deletion causes sperm maturation defects, linking ClC-2 to male fertility .

Pharmacological Modulation

• Lubiprostone: A ClC-2 activator used to treat constipation and ischemia-induced epithelial barrier dysfunction .

Technical Considerations

• Antigen Retrieval: Optimal staining in IHC requires Tris-HCl (pH 10.0) microwave treatment .

• Cross-Reactivity: Some antibodies (e.g., PHY0702A ) target non-channel proteins like clathrin light chains, necessitating careful validation.

Disease Associations