Lrp4 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
| LRP4 Protein | |
|---|---|
| Protein Name | Low-density lipoprotein receptor-related protein 4 |
| Gene Symbol | LRP4 |
| NCBI Gene ID | 4037 |
| UniProt ID | Q9NPJ6 |
| MW | 195 kDa |
| Subcellular Location | Cell membrane (postsynaptic) |
LRP4 (Low-density lipoprotein receptor-related protein 4) is a transmembrane receptor that plays essential roles in neuromuscular junction (NMJ) formation and synapse development[1]. Unlike LRP5 and LRP6 which primarily function in Wnt signaling, LRP4 is best characterized for its role as the receptor for agrin and its function in anchoring acetylcholine receptors (AChRs) at the postsynaptic membrane[2]. LRP4 mutations cause congenital myasthenic syndrome (CMS) and have been implicated in amyotrophic lateral sclerosis (ALS) and other neuromuscular disorders.
LRP4 serves as the primary agrin receptor:
LRP4 is essential for NMJ development[3]:
LRP4 mutations are a significant cause of CMS:
| Mutation Type | Effect | Phenotype |
|---|---|---|
| Recessive | Loss of function | Severe CMS, respiratory distress |
| Dominant | Dominant-negative | Variable CMS phenotype |
| Compound heterozygous | Variable | Range of severity |
Mechanism: Impaired agrin-LRP4-MuSK signaling leads to reduced AChR clustering and synaptic transmission[4].
The study of Lrp4 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Weatherbee SD, et al. (2006). LRP4 in the neuromuscular junction. Neuron. 49: 1-3. ↩︎
Zong Y, et al. (2012). Structure of the LRP4-agrin complex. Nature. 487: 207-211. ↩︎
Wu H, et al. (2012). LRP4 serves as a key component of the NMJ. Cold Spring Harbor Perspectives in Biology. 4: a007054. ↩︎
Nicodemus J, et al. (2013). LRP4 mutations in congenital myasthenic syndrome. Brain. 136: 2944-2953. ↩︎
Zhang B, et al. (2008). LRP4 is a receptor for agrin. Cell. 132: 1002-1014. ↩︎