5b4y

Structural highlights

Disease

[LRP8_HUMAN] Defects in LRP8 are a cause of myocardial infarction type 1 (MCI1) [MIM:608446]. A condition defined by the irreversible necrosis of heart muscle secondary to prolonged ischemia.

Function

[LRP8_HUMAN] Cell surface receptor for Reelin (RELN) and apolipoprotein E (apoE)-containing ligands. LRP8 participates in transmitting the extracellular Reelin signal to intracellular signaling processes, by binding to DAB1 on its cytoplasmic tail. Reelin acts via both the VLDL receptor (VLDLR) and LRP8 to regulate DAB1 tyrosine phosphorylation and microtubule function in neurons. LRP8 has higher affinity for Reelin than VLDLR. LRP8 is thus a key component of the Reelin pathway which governs neuronal layering of the forebrain during embryonic brain development. Binds the endoplasmic reticulum resident receptor-associated protein (RAP). Binds dimers of beta 2-glycoprotein I and may be involved in the suppression of platelet aggregation in the vasculature. Highly expressed in the initial segment of the epididymis, where it affects the functional expression of clusterin and phospholipid hydroperoxide glutathione peroxidase (PHGPx), two proteins required for sperm maturation. May also function as an endocytic receptor.^{[1] [2] [3]}

References

1. ↑ Andersen OM, Benhayon D, Curran T, Willnow TE. Differential binding of ligands to the apolipoprotein E receptor 2. Biochemistry. 2003 Aug 12;42(31):9355-64. PMID:12899622 doi:10.1021/bi034475p
2. ↑ Li X, Kypreos K, Zanni EE, Zannis V. Domains of apoE required for binding to apoE receptor 2 and to phospholipids: implications for the functions of apoE in the brain. Biochemistry. 2003 Sep 9;42(35):10406-17. PMID:12950167 doi:http://dx.doi.org/10.1021/bi027093c
3. ↑ Lutters BC, Derksen RH, Tekelenburg WL, Lenting PJ, Arnout J, de Groot PG. Dimers of beta 2-glycoprotein I increase platelet deposition to collagen via interaction with phospholipids and the apolipoprotein E receptor 2'. J Biol Chem. 2003 Sep 5;278(36):33831-8. Epub 2003 Jun 13. PMID:12807892 doi:10.1074/jbc.M212655200