Megalin

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Megalin
Properties of human protein
Mass / length primary structure 4630 amino acids
Secondary to quaternary structure Transmembrane receptor
Cofactor Ca 2+
Identifier
Gene name LRP2
External IDs
Occurrence
Homology family LDLR-related
Parent taxon Bilateral animals

Megalin (also Low Density Lipoprotein Receptor-Related Protein 2 , LRP2 ) is a protein in the cell membrane of several tissues, a so-called receptor . It is one of two proteins responsible for endocytosis in bilateral animals , and therefore also in humans. Mutations in LRP2 - gene can Megalinmangel and this to proteinuria and rare Donnai-Barrow syndrome , a serious development affecting lead.

Megalin belongs to a family of receptors that have structural similarities to the LDL receptor . At 4630 amino acids , it's a very large protein.

function

Megalin is mainly found in epithelial tissue membranes and together with its partner Cubilin ensures the absorption of many substances into the cell through membrane transport (endocytosis) . Megalin not only binds to cubilin, which itself acts as a receptor for many lipid , hormone and vitamin- transporting complexes. Megalin itself also binds to lipids , blood coagulation factors , VLDL , albumin , lactoferrin , selenoprotein P and clusterin . The Cubilin: Megalin complex is mainly responsible for the absorption of cobalamin in the intestine, of proteins, lipids, calcidiol and iron from the blood, and the retention of most of these substances in the proximal tubular cells .

The cubilin: megalin complex may be necessary to prevent gallstones . Megalin variants are associated with the incidence, course, and effectiveness of prostate cancer therapy . By binding to metallothionein , megalin plays a role in the development of astrocytes .

regulation

The activity and expression of cubilin and megalin is stimulated by tretinoin and is therefore increased in dividing and cancer cells. The expression of megalin in the kidneys increases with age, probably to compensate for the increasing number of defects in the large protein.

Individual evidence

  1. ↑ a b UniProt P98164
  2. ↑ Motoyoshi Y, Matsusaka T, Saito A, et al : Megalin contributes to the early injury of proximal tubule cells during nonselective proteinuria . In: Kidney Int . 74, No. 10, November 2008, pp. 1262-9. doi : 10.1038 / ki.2008.405 . PMID 18769366 .
  3. ^ Baines RJ, Brunskill NJ: The molecular interactions between filtered proteins and proximal tubular cells in proteinuria . In: Nephron Exp. Nephrol. . 110, No. 2, 2008, pp. E67–71. doi : 10.1159 / 000161982 . PMID 18849618 .
  4. ↑ UniProt O60494
  5. ↑ Bento-Abreu A, Velasco A, Polo-Hernández E, Pérez-Reyes PL, Tabernero A, Medina JM: Megalin is a receptor for albumin in astrocytes and is required for the synthesis of the neurotrophic factor oleic acid . In: J. Neurochem. . 106, No. 3, August 2008, pp. 1149-59. doi : 10.1111 / j.1471-4159.2008.05462.x . PMID 18466341 .
  6. ↑ Olson GE, Winfrey VP, Hill KE, Burk RF: Megalin mediates selenoprotein P uptake by kidney proximal tubule epithelial cells . In: J. Biol. Chem. . 283, No. 11, March 2008, pp. 6854-60. doi : 10.1074 / jbc.M709945200 . PMID 18174160 .
  7. ↑ Tsaroucha AK, Chatzaki E, Lambropoulou M, et al : Megalin and cubilin in the human gallbladder epithelium . In: Clin. Exp. Med. . 8, No. 3, September 2008, pp. 165-70. doi : 10.1007 / s10238-008-0174-y . PMID 18791690 .
  8. ↑ Holt SK, Karyadi DM, Kwon EM, Stanford JL, Nelson PS, Ostrander EA: Association of megalin genetic polymorphisms with prostate cancer risk and prognosis . In: Clin. Cancer Res . 14, No. 12, June 2008, pp. 3823-31. doi : 10.1158 / 1078-0432.CCR-07-4566 . PMID 18559602 .
  9. ↑ Ambjørn M, Asmussen JW, Lindstam M, et al : Metallothionein and a peptide modeled after metallothionein, EmtinB, induce neuronal differentiation and survival through binding to receptors of the low-density lipoprotein receptor family . In: J. Neurochem. . 104, No. 1, January 2008, pp. 21-37. doi : 10.1111 / j.1471-4159.2007.05036.x . PMID 17986228 .
  10. ↑ Wicher G, H Aldskogius: megalin deficiency induces critical changes in mouse spinal cord development . In: Neuroreport . 19, No. 5, March 2008, pp. 559-63. doi : 10.1097 / WNR.0b013e3282f94267 . PMID 18388738 .
  11. ↑ Chlon TM, Taffany DA, Welsh J, Rowling MJ: Retinoids modulate expression of the endocytic partners megalin, cubilin, and disabled-2 and uptake of vitamin D-binding protein in human mammary cells . In: J. Nutr. . 138, No. 7, July 2008, pp. 1323-8. PMID 18567755 . PMC 2443692 (free full text).
  12. ↑ Odera K, Goto S, Takahashi R: Age-related change of endocytic receptors megalin and cubilin in the kidney in rats . In: Biogerontology . 8, No. 5, October 2007, pp. 505-15. doi : 10.1007 / s10522-007-9093-7 . PMID 17453355 .

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