LINGO1
Description
The LINGO1 (leucine rich repeat and Ig domain containing 1) is a protein-coding gene located on chromosome 15.
LINGO1, also known as Leucine-rich repeat and Immunoglobin-like domain-containing protein 1 (LINGO-1), is a protein encoded by the LINGO1 gene in humans. It belongs to the leucine-rich repeat protein family, known for their crucial roles in the central nervous system. LINGO-1 is a functional component of the Nogo receptor (RTN4R), also known as the reticulon 4 receptor. It has been proposed that LINGO-1 antagonists, such as BIIB033, could significantly improve and regulate survival after neural injuries caused by the protein.
LINGO-1 is a single-pass type 1 transmembrane protein composed of 614 amino acids. It features a signal sequence of 34 residues, followed by a LRR (leucine-rich repeat) domain, an Ig (immunoglobulin-like) domain, a stalk domain, a transmembrane region, and a short cytoplasmic tail. As a transmembrane protein, it predominantly resides on the cell membrane. Its structure, characterized by a leucine-rich repeat Ig-composite fold, exhibits remarkable stability both in its crystalline form and in solution. The tetrameric structure of LINGO-1 possesses a large surface area facing the cell membrane, suggesting its potential role as an efficient and stable binding platform, facilitating interactions with the NgR, p75, and TROY complex.
The extracellular domain comprises the signal sequence, 11 LRR motifs flanked by N-terminal and C-terminal capping domains, and the Immunoglobulin-like (IgC2) domain.
LINGO1 plays a critical role in inhibiting axonal regeneration by activating the RhoA pathway within the Nogo receptor signaling complex. This inhibition is triggered by myelin-associated factors. Additionally, LINGO1 acts as a negative regulator of oligodendrocyte differentiation and myelination. In collaboration with RTN4 and RTN4R, LINGO1 regulates neuronal precursor cell motility during cortical development.
LINGO1 is also known as LERN1, LRRN6A, MRT64, UNQ201.
