LRP6 Membrane Protein Introduction

Introduction of LRP6

LRP6 (low-density lipoprotein receptor-related protein 6) is a protein that in humans is encoded by the LRP6 gene. It’s a key component of the LRP5/LRP6/Frizzled co-receptor group, and results in transducing signals by Wnt proteins through the canonical Wnt signaling pathway. It shares a similar structure with LRP5. In clinics, LRP6 deficiency can cause increased plasma LDL and triglycerides, hypertension, diabetes and osteoporosis.

Basic Information of LRP6
Protein Name	Low-density lipoprotein receptor-related protein 6
Gene Name	LRP6
Aliases	/
Organism	Homo sapiens (Human)
UniProt ID	O75581
Transmembrane Times	1
Length (aa)	1613
Sequence	MGAVLRSLLACSFCVLLRAAPLLLYANRRDLRLVDATNGKENATIVVGGLEDAAAVDFVFSHGLIYWSDVSEEAIKRTEFNKTESVQNVVVSGLLSPDGLACDWLGEKLYWTDSETNRIEVSNLDGSLRKVLFWQELDQPRAIALDPSSGFMYWTDWGEVPKIERAGMDGSSRFIIINSEIYWPNGLTLDYEEQKLYWADAKLNFIHKSNLDGTNRQAVVKGSLPHPFALTLFEDILYWTDWSTHSILACNKYTGEGLREIHSDIFSPMDIHAFSQQRQPNATNPCGIDNGGCSHLCLMSPVKPFYQCACPTGVKLLENGKTCKDGATELLLLARRTDLRRISLDTPDFTDIVLQLEDIRHAIAIDYDPVEGYIYWTDDEVRAIRRSFIDGSGSQFVVTAQIAHPDGIAVDWVARNLYWTDTGTDRIEVTRLNGTMRKILISEDLEEPRAIVLDPMVGYMYWTDWGEIPKIERAALDGSDRVVLVNTSLGWPNGLALDYDEGKIYWGDAKTDKIEVMNTDGTGRRVLVEDKIPHIFGFTLLGDYVYWTDWQRRSIERVHKRSAEREVIIDQLPDLMGLKATNVHRVIGSNPCAEENGGCSHLCLYRPQGLRCACPIGFELISDMKTCIVPEAFLLFSRRADIRRISLETNNNNVAIPLTGVKEASALDFDVTDNRIYWTDISLKTISRAFMNGSALEHVVEFGLDYPEGMAVDWLGKNLYWADTGTNRIEVSKLDGQHRQVLVWKDLDSPRALALDPAEGFMYWTEWGGKPKIDRAAMDGSERTTLVPNVGRANGLTIDYAKRRLYWTDLDTNLIESSNMLGLNREVIADDLPHPFGLTQYQDYIYWTDWSRRSIERANKTSGQNRTIIQGHLDYVMDILVFHSSRQSGWNECASSNGHCSHLCLAVPVGGFVCGCPAHYSLNADNRTCSAPTTFLLFSQKSAINRMVIDEQQSPDIILPIHSLRNVRAIDYDPLDKQLYWIDSRQNMIRKAQEDGSQGFTVVVSSVPSQNLEIQPYDLSIDIYSRYIYWTCEATNVINVTRLDGRSVGVVLKGEQDRPRAVVVNPEKGYMYFTNLQERSPKIERAALDGTEREVLFFSGLSKPIALALDSRLGKLFWADSDLRRIESSDLSGANRIVLEDSNILQPVGLTVFENWLYWIDKQQQMIEKIDMTGREGRTKVQARIAQLSDIHAVKELNLQEYRQHPCAQDNGGCSHICLVKGDGTTRCSCPMHLVLLQDELSCGEPPTCSPQQFTCFTGEIDCIPVAWRCDGFTECEDHSDELNCPVCSESQFQCASGQCIDGALRCNGDANCQDKSDEKNCEVLCLIDQFRCANGQCIGKHKKCDHNVDCSDKSDELDCYPTEEPAPQATNTVGSVIGVIVTIFVSGTVYFICQRMLCPRMKGDGETMTNDYVVHGPASVPLGYVPHPSSLSGSLPGMSRGKSMISSLSIMGGSSGPPYDRAHVTGASSSSSSSTKGTYFPAILNPPPSPATERSHYTMEFGYSSNSPSTHRSYSYRPYSYRHFAPPTTPCSTDVCDSDYAPSRRMTSVATAKGYTSDLNYDSEPVPPPPTPRSQYLSAEENYESCPPSPYTERSYSHHLYPPPPSPCTDSS

Function of LRP6 Membrane Protein

LRP6 (Low-density lipoprotein receptor-related protein 6) is a transmembrane protein with only 1 transmembrane domain. It is a key component of LRP5/LRP6/Frizzled complex to transduce signals by Wnt proteins through canonical Wnt signaling pathway. The deep mechanism is inducing aggregation of receptor-ligand complexes into ribosome-sized signalsomes. Also, LRP6 can be a cell surface coreceptor of Wnt/beta-catenin signaling to play an important role in bone formation. In addition, the Wnt-induced Fzd/LRP6 complex can recruit DVL2 polymers to the plasma membrane, and they can recruit the AXIN1/GSK3B to the cell surface to promote the signalsomes formation and inhibit phosphorylation and destruction of beta-catenin. Moreover, LRP6 is required for posterior patterning of the epiblast during gastrulation. In clinics, it has been reported that LRP6 is associated with diseases including increased plasma LDL and triglycerides, hypertension, diabetes and osteoporosis. The inhibitor of LRP6 can be as a promising therapeutic antagonist in osteoporosis clinical trials.

Fig.1 The LRP family including LRP6 (Andersen, 2011)

Application of LRP6 Membrane Protein in Literature

Nayak G., et al. Developmental vascular regression is regulated by a Wnt/β-catenin, MYC and CDKN1A pathway that control cell proliferation and cell death. Development. 2018, 145(12). PubMed ID: 29777010

This article shows that the Wnt pathway co-receptors LRP5 and LRP6 have overlapping activities that mediate the Wnt/β-catenin signaling in hyaloid vascular endothelial cells (VECs).
Zhou J., et al. Nanorod diameter modulated osteogenic activity of hierarchical micropore/nanorod-patterned coatings via a Wnt/β-catenin pathway. Nanomedicine. 2018, 14(5):1719-1731. PubMed ID: 29665441

This article demonstrates that MNRs activate the cellular Wnt/β-catenin pathway by increasing the expression of Wnt3a and LRP6 and decreasing the expression of Wnt/β-catenin pathway antagonists.
Ji C., et al. Capillary morphogenesis gene 2 maintains gastric cancer stem-like cell phenotype by activating a Wnt/β-catenin pathway. Oncogene. 2018, 37(29):3953-3966. PubMed ID: 29662192

This article indicates that CMG2 interacts with LRP6 in GCSLCs to activate a Wnt/β-catenin pathway. This demonstrates that CMG2 can serve as a new prognostic indicator for human GC therapy.
Yu Y., et al. Osteogenesis potential of different titania nanotubes in oxidative stress microenvironment. Biomaterials. 2018, 167:44-57. PubMed ID: 29554480

This article shows that Wnt signals including Wnt3a, Wnt5a, Lrp5, Lrp6 and β-catenin play a critical role in promoting osteogenic differentiation of osteoblasts under oxidative condition.
Chen Z., et al. Cardiomyocyte-Restricted Low Density Lipoprotein Receptor-Related Protein 6 (LRP6) Deletion Leads to Lethal Dilated Cardiomyopathy Partly Through Drp1 Signaling. Theranostics. 2018, 8(3):627-643. PubMed ID: 29344294

This article shows LRP6 expression is associated with heart failure progression through Drp1 signaling.

LRP6 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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