Disease relevance of LRP4

• The identification of Lrp4 as a crucial factor for NMJ formation may have implications for human neuromuscular diseases such as myasthenia syndromes [1].
• Targeted and naturally occurring mutations in the murine Megf7/Lrp4 gene, a putative coreceptor in the Wnt signaling pathway, cause polysyndactyly in the rodent [2].
• LRP4 mutations happens in Cenani-Lenz Syndrome [3].

High impact information on LRP4

• The reason for this developmental abnormality is apparent as early as embryonic day 9.5 when the apical ectodermal ridge (AER), the principal site of Megf7 expression at the distal edge of the embryonic limb bud, forms abnormally in the absence of Megf7 [4].
• Abnormal signaling from the AER precedes ectopic chondrocyte condensation and subsequent fusion and duplication of digits in the Megf7 knockouts [4].
• Our data show that Lrp4 is required during the earliest events in postsynaptic neuromuscular junction (NMJ) formation and suggest that it acts in the early, nerveindependent steps of NMJ assembly [1].
• Lrp4 is expressed in multiple tissues in the mouse, and is important for the proper development and morphogenesis of limbs, ectodermal organs, lungs and kidneys [1].
• Lrp4-mutant mice die at birth with defects in both presynaptic and postsynaptic differentiation, including aberrant motor axon growth and branching, a lack of acetylcholine receptor and postsynaptic protein clustering, and a failure to express postsynaptic genes selectively by myofiber synaptic nuclei [1].

Biological context of LRP4

• Pathologies observed in the mutant mice provide insight into understanding the function(s) of LRP4 as a negative regulator of the Wnt-beta-catenin signaling pathway and may help identify the genetic basis for common human disorders with similar phenotypes [5].
• Low-density lipoprotein receptor-related protein 4 (Lrp4) is a member of a family of structurally related, single-pass transmembrane proteins that carry out a variety of functions in development and physiology, including signal transduction and receptor-mediated endocytosis [1].

Anatomical context of LRP4

• The mRNA of LRP4 was localized to dendrites, as well as somas, of neuronal cells, and the full-length protein of 250 kDa was highly concentrated in the brain and localized to various subcellular compartments in the brain, including synaptic fractions [6].

Associations of LRP4 with chemical compounds

• LRP4 protein interacted with postsynaptic scaffold proteins such as postsynaptic density (PSD)-95 via its C-terminal tail sequence, and associated with N-methyl-D-aspartate (NMDA)-type glutamate receptor subunit [6].

Other interactions of LRP4

• Also, the LDL receptor and LDL receptor-related protein (LRP-4) mRNAs were unchanged [7].

References