LRP4 Membrane Protein Introduction

Introduction of LRP4

LRP4, low-density lipoprotein receptor-related protein 4, is a protein that in humans is encoded by the LRP4 gene. It’s also known as multiple epidermal growth factor-like domains 7 (MEGF7). LRP-4 is a member of the lipoprotein receptor-related protein family and might be a regulator of Wnt signaling pathway. In the clinic, it has been found that the mutations in this gene are associated with Cenani Lenz syndactylism.

Basic Information of LRP4
Protein Name	Low-density lipoprotein receptor-related protein 4
Gene Name	LRP4
Aliases	Multiple epidermal growth factor-like domains 7 (MEGF7), KIAA0816, LRP10
Organism	Homo sapiens (Human)
UniProt ID	O75096
Transmembrane Times	1
Length (aa)	1905
Sequence	MRRQWGALLLGALLCAHGLASSPECACGRSHFTCAVSALGECTCIPAQWQCDGDNDCGDHSDEDGCILPTCSPLDFHCDNGKCIRRSWVCDGDNDCEDDSDEQDCPPRECEEDEFPCQNGYCIRSLWHCDGDNDCGDNSDEQCDMRKCSDKEFRCSDGSCIAEHWYCDGDTDCKDGSDEENCPSAVPAPPCNLEEFQCAYGRCILDIYHCDGDDDCGDWSDESDCSSHQPCRSGEFMCDSGLCINAGWRCDGDADCDDQSDERNCTTSMCTAEQFRCHSGRCVRLSWRCDGEDDCADNSDEENCENTGSPQCALDQFLCWNGRCIGQRKLCNGVNDCGDNSDESPQQNCRPRTGEENCNVNNGGCAQKCQMVRGAVQCTCHTGYRLTEDGHTCQDVNECAEEGYCSQGCTNSEGAFQCWCETGYELRPDRRSCKALGPEPVLLFANRIDIRQVLPHRSEYTLLLNNLENAIALDFHHRRELVFWSDVTLDRILRANLNGSNVEEVVSTGLESPGGLAVDWVHDKLYWTDSGTSRIEVANLDGAHRKVLLWQNLEKPRAIALHPMEGTIYWTDWGNTPRIEASSMDGSGRRIIADTHLFWPNGLTIDYAGRRMYWVDAKHHVIERANLDGSHRKAVISQGLPHPFAITVFEDSLYWTDWHTKSINSANKFTGKNQEIIRNKLHFPMDIHTLHPQRQPAGKNRCGDNNGGCTHLCLPSGQNYTCACPTGFRKISSHACAQSLDKFLLFARRMDIRRISFDTEDLSDDVIPLADVRSAVALDWDSRDDHVYWTDVSTDTISRAKWDGTGQEVVVDTSLESPAGLAIDWVTNKLYWTDAGTDRIEVANTDGSMRTVLIWENLDRPRDIVVEPMGGYMYWTDWGASPKIERAGMDASGRQVIISSNLTWPNGLAIDYGSQRLYWADAGMKTIEFAGLDGSKRKVLIGSQLPHPFGLTLYGERIYWTDWQTKSIQSADRLTGLDRETLQENLENLMDIHVFHRRRPPVSTPCAMENGGCSHLCLRSPNPSGFSCTCPTGINLLSDGKTCSPGMNSFLIFARRIDIRMVSLDIPYFADVVVPINITMKNTIAIGVDPQEGKVYWSDSTLHRISRANLDGSQHEDIITTGLQTTDGLAVDAIGRKVYWTDTGTNRIEVGNLDGSMRKVLVWQNLDSPRAIVLYHEMGFMYWTDWGENAKLERSGMDGSDRAVLINNNLGWPNGLTVDKASSQLLWADAHTERIEAADLNGANRHTLVSPVQHPYGLTLLDSYIYWTDWQTRSIHRADKGTGSNVILVRSNLPGLMDMQAVDRAQPLGFNKCGSRNGGCSHLCLPRPSGFSCACPTGIQLKGDGKTCDPSPETYLLFSSRGSIRRISLDTSDHTDVHVPVPELNNVISLDYDSVDGKVYYTDVFLDVIRRADLNGSNMETVIGRGLKTTDGLAVDWVARNLYWTDTGRNTIEASRLDGSCRKVLINNSLDEPRAIAVFPRKGYLFWTDWGHIAKIERANLDGSERKVLINTDLGWPNGLTLDYDTRRIYWVDAHLDRIESADLNGKLRQVLVSHVSHPFALTQQDRWIYWTDWQTKSIQRVDKYSGRNKETVLANVEGLMDIIVVSPQRQTGTNACGVNNGGCTHLCFARASDFVCACPDEPDSRPCSLVPGLVPPAPRATGMSEKSPVLPNTPPTTLYSSTTRTRTSLEEVEGRCSERDARLGLCARSNDAVPAAPGEGLHISYAIGGLLSILLILVVIAALMLYRHKKSKFTDPGMGNLTYSNPSYRTSTQEVKIEAIPKPAMYNQLCYKKEGGPDHNYTKEKIKIVEGICLLSGDDAEWDDLKQLRSSRGGLLRDHVCMKTDTVSIQASSGSLDDTETEQLLQEEQSECSSVHTAATPERRGSLPDTGWKHERKLSSESQV

Function of LRP4 Membrane Protein

LRP4 (Low-density lipoprotein receptor-related protein 4) is also known as MEGF7, KIAA0816 and LRP10. It can mediate SOST-dependent inhibition of bone formation and function as a specific facilitator of SOST-mediated inhibition of Wnt signaling. Also, it plays a key role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between the motor neuron and skeletal muscle. It directly binds to AGRIN and is recruited to the MUSK signaling complex. Except for these, it can mediate the AGRIN-induced phosphorylation of MUSK. In addition, it 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, it has been proposed to function as a cell surface endocytic receptor binding and internalizing extracellular ligands for degradation by lysosomes. Moreover, LRP4 may play an essential role in the process of digit differentiation. LRP4 controls osteoclastogenesis, and it mediates the pathophysiological mechanism of high-bone-mass disorders.

Fig.1 The LRP family (Andersen, 2006)

Application of LRP4 Membrane Protein in Literature

Ye X.C., et al. Astrocytic Lrp4 (Low-Density Lipoprotein Receptor-Related Protein 4) Contributes to Ischemia-Induced Brain Injury by Regulating ATP Release and Adenosine-A_2AR (Adenosine A2A Receptor) Signaling. Stroke. 2018, 49(1):165-174. PubMed ID: 29212737

This article shows that astrocytic LRP4 plays a critical role in ischemic brain injury response.
Karakatsani A., et al. Neuronal LRP4 regulates synapse formation in the developing CNS. Development. 2017, 144(24):4604-4615. PubMed ID: 29061639

This article demonstrates that neuronal LRP4 plays an essential and novel role in dendritic development and synaptogenesis in the CNS.
Ahn Y., et al. Multiple modes of Lrp4 function in modulation of Wnt/β-catenin signaling during tooth development. Development. 2017, 144(15):2824-2836. PubMed ID: 28694256

This article indicates that Lrp4 can modulate Wnt/β-catenin signaling through interaction with Wnt ligands and antagonists in a context-dependent manner.
Boudin E., et al. The Lrp4R1170Q Homozygous Knock-In Mouse Recapitulates the Bone Phenotype of Sclerosteosis in Humans. J Bone Miner Res. 2017, 32(8):1739-1749. PubMed ID: 28477420

This article shows that mutations in LRP4 can cause human sclerosteosis phenotype through R1170Q, and the model can be used for further investigation of the mechanism by which LRP4 regulates bone formation.
Xiong L., et al. Osteoblastic Lrp4 promotes osteoclastogenesis by regulating ATP release and adenosine-A2AR signaling. J Cell Biol. 2017, 216(3):761-778. PubMed ID: 28193701

This article shows a novel mechanism by which osteoblastic LRP4 controls osteoclastogenesis. It also identifies a new pathophysiological mechanism of high-bone-mass disorders.

LRP4 Preparation Options

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Reference

Andersen O M and Willnow T E. (2006). Lipoprotein receptors in Alzheimer's disease. Trends Neurosci. 29(12):687-94.

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