CDB25:0003155 APP — LRP4

Experimentally validated in Mouse; Orthology-inferred in Human, Rat, Frog, Zebrafish, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep

Title

Journal:; Year Published:

Abstract

APP interacts with LRP4 and agrin to coordinate the development of the neuromuscular junction in mice.

eLife, 2013; PubMed, Mus Musculus App — Mus Musculus Lrp4
ABSTRACT: ApoE, ApoE receptors and APP cooperate in the pathogenesis of Alzheimer's disease. Intriguingly, the ApoE receptor LRP4 and APP are also required for normal formation and function of the neuromuscular junction (NMJ). In this study, we show that APP interacts with LRP4, an obligate co-receptor for muscle-specific tyrosine kinase (MuSK). Agrin, a ligand for LRP4, also binds to APP and co-operatively enhances the interaction of APP with LRP4. In cultured myotubes, APP synergistically increases agrin-induced acetylcholine receptor (AChR) clustering. Deletion of the transmembrane domain of LRP4 (LRP4 ECD) results in growth retardation of the NMJ, and these defects are markedly enhanced in APP(-/-);LRP4(ECD/ECD) mice. Double mutant NMJs are significantly reduced in size and number, resulting in perinatal lethality. Our findings reveal novel roles for APP in regulating neuromuscular synapse formation through hetero-oligomeric interaction with LRP4 and agrin and thereby provide new insights into the molecular mechanisms that govern NMJ formation and maintenance. DOI:http://dx.doi.org/10.7554/eLife.00220.001.
Basic Information on APP
Ligand Name: amyloid beta precursor protein
Other Symbols: AD1, alpha-sAPP
Ligand Location: secreted based on hpa, perplexity, uniprot, cell membrane based on perplexity, uniprot
HGNC Gene Symbol Report: APP
GeneCards: APP
HGNC Gene Group: Receptor ligands
Functional Annotations for APP
Gene Ontologies: PAN-GO, AmiGO 2
Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)
Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)
Interactions with other Receptors for APP
APP — CD74 ・ APP — FPR2 ・ APP — GPC1 ・ APP — LRP1 ・ APP — ADRA2A ・ APP — AGER ・ APP — APLP1 ・ APP — APLP2 ・ APP — CNTN3 ・ APP — CNTN4 ・ APP — CNTN5 ・ APP — DCC ・ APP — LRP10 ・ APP — LRP2 ・ APP — LRP6 ・ APP — NOTCH1 ・ APP — NOTCH2 ・ APP — RPSA ・ APP — TRPC6
Basic Information on LRP4
Receptor Name: LDL receptor related protein 4
Other Symbols: MEGF7, CLSS, LRP-4, SOST2
Receptor Location: cell membrane based on perplexity, uniprot
HGNC Gene Symbol Report: LRP4
GeneCards: LRP4
Functional Annotations for LRP4
Gene Ontologies: PAN-GO, AmiGO 2
Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)
Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)
Interactions with other Ligands for LRP4
AGRN — LRP4 ・ DKK1 — LRP4 ・ SOST — LRP4 ・ SOSTDC1 — LRP4 ・ APOE — LRP4 ・ COLQ — LRP4
← CDB25 APP LRP2
CDB25 APP LRP6 →