Lrp4
Function
Mediates SOST-dependent inhibition of bone formation. Functions as a specific facilitator of SOST-mediated inhibition of Wnt signaling. Plays a key role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between motor neuron and skeletal muscle. Directly binds AGRIN and recruits it to the MUSK signaling complex. Mediates the AGRIN-induced phosphorylation of MUSK, the kinase of the complex. The activation of MUSK in myotubes induces the formation of NMJ by regulating different processes including the transcription of specific genes and the clustering of AChR in the postsynaptic membrane. Alternatively, may be involved in the negative regulation of the canonical Wnt signaling pathway, being able to antagonize the LRP6-mediated activation of this pathway. More generally, has been proposed to function as a cell surface endocytic receptor binding and internalizing extracellular ligands for degradation by lysosomes. Plays an essential role in the process of digit differentiation (PubMed:16517118).
Involvement in disease
Defects in Lrp4 are the cause of digitation anormale (dan) phenotype, this mutation is the consequence of a retroviral insertion. Dan mice shown growth retardation in 10-day-old mice dan/dan and polysyndactyly (PubMed:16517118). Defects in Lrp4 are the cause of malformed digits (mdig) phenotype. It is a spontaneous, autosomal recessive mutation resulting in polysyndactyly (PubMed:16517118).
Post-translational modifications
N-glycosylation is required for cell surface location.
Sequence Similarities
Belongs to the LDLR family.
Cellular localization
- Cell membrane
- Single-pass type I membrane protein
Alternative names
Kiaa0816, Lrp4, Low-density lipoprotein receptor-related protein 4, LRP-4, LDLR dan