Definition
The reeler domain, also referred to as the Reelin repeat, is a conserved protein‑binding module of approximately 45–60 amino acids that occurs in the extracellular matrix protein Reelin and in several other secreted proteins. It functions primarily in the regulation of neuronal migration and positioning during brain development.
Overview
Reelin is a large secreted glycoprotein (~4,200 amino acids) essential for proper lamination of the cerebral cortex, hippocampus, and cerebellum. The protein comprises eight tandemly arranged reeler domains, each contributing to the overall structural integrity and interaction capacity of Reelin. The reeler domain mediates homophilic and heterophilic protein–protein interactions, facilitating the activation of downstream signaling pathways through binding to the lipoprotein receptors VLDLR and ApoER2. Similar domains have been identified in other extracellular proteins, suggesting a broader role in cell adhesion and signaling.
Etymology / Origin
The name derives from the reeler mouse mutant, first described in the 1950s. Mice carrying the reeler mutation exhibit severe defects in neuronal migration, leading to a characteristic “reeling” gait. Subsequent molecular cloning revealed that the mutation affected the Reelin gene, and the repeating units within the protein were subsequently named “reeler domains” in reference to the phenotype.
Characteristics
- Length: Typically 45–60 residues per repeat.
- Conserved motif: Contains a characteristic pattern of cysteine residues (often C‑X₃‑C) that form disulfide bonds, stabilizing a β‑sheet-rich fold.
- Structure: Predicted to adopt a compact β‑sandwich architecture, as supported by X‑ray crystallography of isolated repeats.
- Distribution: Present in all eight repeats of Reelin; also found in a limited set of other secreted proteins across vertebrates.
- Function: Facilitates extracellular interactions that trigger intracellular signaling cascades (e.g., Dab1 phosphorylation) critical for neuronal layer formation.
- Evolution: The domain is highly conserved among mammals, with orthologous repeats identified in avian and reptilian Reelin homologs.
Related Topics
- Reelin – the parent protein containing reeler domains.
- Neuronal migration – developmental process regulated by Reelin signaling.
- VLDLR and ApoER2 – lipoprotein receptors that bind Reelin.
- Dab1 – intracellular adaptor phosphorylated upon Reelin receptor activation.
- Extracellular matrix proteins – broader class of secreted proteins that may contain reeler-like domains.
- Protein domains – modular units of protein structure and function.