LIN7A operates within multiprotein complexes, particularly with:
This network enables:
Polarized trafficking of receptors (EGFR, NMDA) to specific membrane domains
Synaptic vesicle exocytosis coordination via CASK interaction
Embryonic expression: Detected from E13.5 in mice, increasing through corticogenesis
Migration defects: LIN7A knockdown delays neuronal positioning in cortical layers (60% deficient neurons in intermediate zone at P2)
Axonal guidance: Silencing disrupts corpus callosum formation (50% reduction in contralateral projections)
14 Mb deletions encompassing LIN7A correlate with:
Overexpression induces:
Human LIN7A (1-233 aa) expressed in E. coli:
In utero electroporation (mouse): 65% migration defect rescue via shRNA
3D mammary acini (MCF10A): LIN7A overexpression causes:
Condition | Mechanism | Therapeutic Target Potential |
---|---|---|
Intellectual disability | Impaired NMDA receptor trafficking | GRIN2B/LIN7A interaction modulators |
Breast cancer | Polarity loss → metastasis | LIN7A-EGFR axis inhibitors |
Epilepsy | Synaptic vesicle mislocalization | CASK/LIN7A complex stabilizers |
Structural studies: Cryo-EM analysis of LIN7A-CASK-APBA1 tripartite complex
Therapeutic development:
Peptide disruptors of LIN7A-KIF17 interaction (tested in vitro)
CRISPR-based LIN7A restoration in 12q21-deletion models
Biomarker potential: Serum LIN7A levels correlate with breast cancer metastasis (AUC = 0.82 in preliminary studies)
LIN7A comprises one L27 domain and one PDZ (DHR) domain . These domains are crucial for its function in cellular processes. The L27 domain is involved in protein-protein interactions, while the PDZ domain plays a role in binding to specific sequences in other proteins, facilitating the formation of protein complexes at the cell membrane .
The primary function of LIN7A is to maintain the polarized distribution of membrane proteins. This is essential for the proper functioning of epithelial cells and neurons. By interacting with other proteins, LIN7A helps to anchor channels and receptors at specific locations on the cell membrane, ensuring that they are correctly positioned to carry out their functions .
Recombinant LIN7A is produced in Escherichia coli and is a single, non-glycosylated polypeptide chain containing 256 amino acids, with a molecular mass of 28.4 kDa . It is fused to a 23 amino acid His-tag at the N-terminus, which facilitates its purification using chromatographic techniques . The recombinant protein is typically used in research to study its function and interactions with other proteins.
Recombinant LIN7A is valuable in various research applications, including: