CD91

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Modelo da LRP1 (baseado en PDB 1cr8).

O CD91 (cluster de diferenciación 91) ou proteína 1 relacionada co receptor da lipoproteína de baixa densidade (LRP1, Low density lipoprotein receptor-related protein 1), tamén chamada receptor de alfa-2-macroglobulina (A2MR), ou receptor de apolipoproteína E (APOER), é unha proteína da superficie celular de certas células, que forma un receptor implicado na endocitose mediada por receptor. Nos humanos está codificado no xene LRP1 do cromosoma 12.[1][2]

Características[editar | editar a fonte]

A LRP1 sinteízase como un precursor longo glicoproteico, que é procesado na rede trans-Golgi polo encima furina, xerando unha subunidade alfa e outra beta máis pequena de 85 kDa, que permanecen ligadas non covalentemente durante o seu transporte á membrana plasmática. A fosforilación da cola da LRP1 regula a introdución do ligando na célula e a transdución de sinais.[3]

Función[editar | editar a fonte]

A LRP1 está implicada en varios procesos celulares, como a sinalización intracelular, homeostase lipídica, e eliminación de células apoptóticas.

LRP1 e a enfermidade de Alzheimer[editar | editar a fonte]

As neuronas precisan colesterol para funcionar. O colesterol é importado ao interior da neurona pola apolipoproteína E (apoE) por medio de receptores LRP1 da superficie celular. A expresión do receptor de lipoproteínas LRP1 regula os niveis de apoE e colesterol no sistema nervioso central. A clivaxe feita polo encima gamma-secretase da proteína precursora amiloide é importante na regulación do metabolismo da apoE e do colesterol a través do LRP1, o que establece unha vinculación entre a proteína precursora amiloide e a apoE, que son os dous maiores determinantes do Alzheimer.[4]

Algúns estudos atoparon que o LRP media a endocitose e degradación da proteína precursora amiloide segregada[5]. Outros estudos indican que a alfa-2 macroglobulina (A2M), por medio do LRP, media a eliminación do amiloide beta xerado pola proteína precursora amiloide, que é o principal compoñente das placas amiloides na enfermidade de Alzheimer.[6]

Interaccións[editar | editar a fonte]

O LRP1 ou CD91 interacciona con: apolipoproteína E,[7][8] lipoproteína lipase,[9][10][11] receptor de uroquinase,[12] MAPK8IP2,[13] activador do plasminóxeno dos tecidos,[14][15] trombospondina 1,[16][17][18] SYNJ2BP,[13] DLG4,[13] NOS1AP,[13] calreticulina,[19] APBB1,[20] ITGB1BP1,[13] MAPK8IP1,[13] GIPC1[13] e SHC1.[21][22]

Notas[editar | editar a fonte]

  1. Herz J, Hamann U, Rogne S, Myklebost O, Gausepohl H, Stanley KK (December 1988). "Surface location and high affinity for calcium of a 500-kd liver membrane protein closely related to the LDL-receptor suggest a physiological role as lipoprotein receptor". EMBO J. 7 (13): 4119–27. PMC 455121. PMID 3266596. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=455121.
  2. Myklebost O, Arheden K, Rogne S, Geurts van Kessel A, Mandahl N, Herz J, Stanley K, Heim S, Mitelman F (July 1989). "The gene for the human putative apoE receptor is on chromosome 12 in the segment q13-14". Genomics 5 (1): 65–9. DOI:10.1016/0888-7543(89)90087-6. PMID 2548950.
  3. OMIM 107770 [1]
  4. Liu Q, Zerbinatti CV, Zhang J, Hoe HS, Wang B, Cole SL, Herz J, Muglia L, Bu G. et al. (2007). "Amyloid precursor protein regulates brain apolipoprotein E and cholesterol metabolism through lipoprotein receptor LRP1". Neuron 56 (1): 66–78. DOI:10.1016/j.neuron.2007.08.008. PMC 2045076. PMID 17920016. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2045076.
  5. Kounnas, M. Z., Moir, R. D., Rebeck, G. W., Bush, A. I., Argraves, W. S., Tanzi, R. E., Hyman, B. T., Strickland, D. K. LDL receptor-related protein, a multifunctional ApoE receptor, binds secreted beta-amyloid precursor protein and mediates its degradation. Cell 82: 331-340, 1995. PMID 7543026. [2]
  6. Narita, M., Holtzman, D. M., Schwartz, A. L., Bu, G. Alpha-2-macroglobulin complexes with and mediates the endocytosis of beta-amyloid peptide via cell surface low-density lipoprotein receptor-related protein. J. Neurochem. 69: 1904-1911, 1997. PMID 9349534. [3]
  7. Poswa M (March 1977). "[Team growth by acquiring an apprentice]". Quintessenz J 7 (3): 21–3. PMID 277965.
  8. Kowal RC, Herz J, Goldstein JL, Esser V, Brown MS (August 1989). "Low density lipoprotein receptor-related protein mediates uptake of cholesteryl esters derived from apoprotein E-enriched lipoproteins". Proc. Natl. Acad. Sci. U.S.A. 86 (15): 5810–4. DOI:10.1073/pnas.86.15.5810. PMC 297720. PMID 2762297. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=297720.
  9. Williams, S E; Inoue I, Tran H, Fry G L, Pladet M W, Iverius P H, Lalouel J M, Chappell D A, Strickland D K (March 1994). "The carboxyl-terminal domain of lipoprotein lipase binds to the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP) and mediates binding of normal very low density lipoproteins to LRP". J. Biol. Chem. (UNITED STATES) 269 (12): 8653–8. ISSN 0021-9258. PMID 7510694.
  10. Nykjaer, A; Nielsen M, Lookene A, Meyer N, Røigaard H, Etzerodt M, Beisiegel U, Olivecrona G, Gliemann J (December 1994). "A carboxyl-terminal fragment of lipoprotein lipase binds to the low density lipoprotein receptor-related protein and inhibits lipase-mediated uptake of lipoprotein in cells". J. Biol. Chem. (UNITED STATES) 269 (50): 31747–55. ISSN 0021-9258. PMID 7989348.
  11. Chappell, D A; Fry G L, Waknitz M A, Iverius P H, Williams S E, Strickland D K (December 1992). "The low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor binds and mediates catabolism of bovine milk lipoprotein lipase". J. Biol. Chem. (UNITED STATES) 267 (36): 25764–7. ISSN 0021-9258. PMID 1281473.
  12. Czekay, R P; Kuemmel T A, Orlando R A, Farquhar M G (May. 2001). "Direct binding of occupied urokinase receptor (uPAR) to LDL receptor-related protein is required for endocytosis of uPAR and regulation of cell surface urokinase activity". Mol. Biol. Cell (United States) 12 (5): 1467–79. ISSN 1059-1524. PMC 34598. PMID 11359936. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=34598.
  13. 13,0 13,1 13,2 13,3 13,4 13,5 13,6 Gotthardt, M; Trommsdorff M, Nevitt M F, Shelton J, Richardson J A, Stockinger W, Nimpf J, Herz J (August 2000). "Interactions of the low density lipoprotein receptor gene family with cytosolic adaptor and scaffold proteins suggest diverse biological functions in cellular communication and signal transduction". J. Biol. Chem. (UNITED STATES) 275 (33): 25616–24. DOI:10.1074/jbc.M000955200. ISSN 0021-9258. PMID 10827173.
  14. Zhuo, M; Holtzman D M, Li Y, Osaka H, DeMaro J, Jacquin M, Bu G (January 2000). "Role of tissue plasminogen activator receptor LRP in hippocampal long-term potentiation". J. Neurosci. (UNITED STATES) 20 (2): 542–9. PMID 10632583.
  15. Orth, K; Madison E L, Gething M J, Sambrook J F, Herz J (August 1992). "Complexes of tissue-type plasminogen activator and its serpin inhibitor plasminogen-activator inhibitor type 1 are internalized by means of the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 89 (16): 7422–6. DOI:10.1073/pnas.89.16.7422. ISSN 0027-8424. PMC 49722. PMID 1502153. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=49722.
  16. Wang, Shuxia; Herndon Mary E, Ranganathan Sripriya, Godyna Svetlana, Lawler Jack, Argraves W Scott, Liau Gene (March 2004). "Internalization but not binding of thrombospondin-1 to low density lipoprotein receptor-related protein-1 requires heparan sulfate proteoglycans". J. Cell. Biochem. (United States) 91 (4): 766–76. DOI:10.1002/jcb.10781. ISSN 0730-2312. PMID 14991768.
  17. Mikhailenko, I; Krylov D, Argraves K M, Roberts D D, Liau G, Strickland D K (March 1997). "Cellular internalization and degradation of thrombospondin-1 is mediated by the amino-terminal heparin binding domain (HBD). High affinity interaction of dimeric HBD with the low density lipoprotein receptor-related protein". J. Biol. Chem. (UNITED STATES) 272 (10): 6784–91. DOI:10.1074/jbc.272.10.6784. ISSN 0021-9258. PMID 9045712.
  18. Godyna, S; Liau G, Popa I, Stefansson S, Argraves W S (June 1995). "Identification of the low density lipoprotein receptor-related protein (LRP) as an endocytic receptor for thrombospondin-1". J. Cell Biol. (UNITED STATES) 129 (5): 1403–10. DOI:10.1083/jcb.129.5.1403. ISSN 0021-9525. PMC 2120467. PMID 7775583. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2120467.
  19. Orr, Anthony Wayne; Pedraza Claudio E, Pallero Manuel Antonio, Elzie Carrie A, Goicoechea Silvia, Strickland Dudley K, Murphy-Ullrich Joanne E (June 2003). "Low density lipoprotein receptor-related protein is a calreticulin coreceptor that signals focal adhesion disassembly". J. Cell Biol. (United States) 161 (6): 1179–89. DOI:10.1083/jcb.200302069. ISSN 0021-9525. PMC 2172996. PMID 12821648. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2172996.
  20. Trommsdorff, M; Borg J P, Margolis B, Herz J (December 1998). "Interaction of cytosolic adaptor proteins with neuronal apolipoprotein E receptors and the amyloid precursor protein". J. Biol. Chem. (UNITED STATES) 273 (50): 33556–60. DOI:10.1074/jbc.273.50.33556. ISSN 0021-9258. PMID 9837937.
  21. Barnes, Helen; Ackermann Elizabeth J, van der Geer Peter (June 2003). "v-Src induces Shc binding to tyrosine 63 in the cytoplasmic domain of the LDL receptor-related protein 1". Oncogene (England) 22 (23): 3589–97. DOI:10.1038/sj.onc.1206504. ISSN 0950-9232. PMID 12789267.
  22. Loukinova, Elena; Ranganathan Sripriya, Kuznetsov Sergey, Gorlatova Natalia, Migliorini Mary M, Loukinov Dmitri, Ulery Paula G, Mikhailenko Irina, Lawrence Daniel A, Strickland Dudley K (May. 2002). "Platelet-derived growth factor (PDGF)-induced tyrosine phosphorylation of the low density lipoprotein receptor-related protein (LRP). Evidence for integrated co-receptor function between LRP and the PDGF". J. Biol. Chem. (United States) 277 (18): 15499–506. DOI:10.1074/jbc.M200427200. ISSN 0021-9258. PMID 11854294.

Véxase tamén[editar | editar a fonte]

Outros artigos[editar | editar a fonte]

  • Li Z, Dai J, Zheng H, et al. (2002). "An integrated view of the roles and mechanisms of heat shock protein gp96-peptide complex in eliciting immune response.". Front. Biosci. 7: d731–51. PMID 11861214.
  • van der Geer P (2002). "Phosphorylation of LRP1: regulation of transport and signal transduction.". Trends Cardiovasc. Med. 12 (4): 160–5. DOI:10.1016/S1050-1738(02)00154-8. PMID 12069755.
  • May P, Herz J (2004). "LDL receptor-related proteins in neurodevelopment.". Traffic 4 (5): 291–301. DOI:10.1034/j.1600-0854.2003.00086_4_5.x. PMID 12713657.
  • Llorente-Cortés V, Badimon L (2005). "LDL receptor-related protein and the vascular wall: implications for atherothrombosis.". Arterioscler. Thromb. Vasc. Biol. 25 (3): 497–504. DOI:10.1161/01.ATV.0000154280.62072.fd. PMID 15705932.
  • Huang SS, Huang JS (2005). "TGF-beta control of cell proliferation.". J. Cell. Biochem. 96 (3): 447–62. DOI:10.1002/jcb.20558. PMID 16088940.
  • Lillis AP, Mikhailenko I, Strickland DK (2005). "Beyond endocytosis: LRP function in cell migration, proliferation and vascular permeability.". J. Thromb. Haemost. 3 (8): 1884–93. DOI:10.1111/j.1538-7836.2005.01371.x. PMID 16102056.

Ligazóns externas[editar | editar a fonte]

  • MeshName - CD91+Antigen [4]