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CD2-Associated Protein (CD2AP)

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Book cover Genetic Variants in Alzheimer's Disease

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Abstract

Genome-wide association studies have implicated the cytoplasmic scaffold CD2-associated protein (CD2AP) in Alzheimer’s disease. Although this association requires independent replication, mechanistically it is involved in recognised disease pathways; immune system function and endocytosis. Currently there is little research into the role of CD2AP in healthy or disease brain tissue, which will be essential to translate the genetic data in the future.

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References

  1. Dustin ML, Olszowy MW, Holdorf AD, Li J, Bromley S, Desai N et al (1998) A novel adaptor protein orchestrates receptor patterning and cytoskeletal polarity in T-cell contacts. Cell 94:667–677

    Article  PubMed  CAS  Google Scholar 

  2. Monzo P, Gauthier NC, Keslair F, Loubat A, Field CM, Le Marchand-Brustel Y et al (2005) Clues to CD2-associated protein involvement in cytokinesis. Mol Biol Cell 16(6):2891–2902

    Article  PubMed  CAS  Google Scholar 

  3. Take H, Watanabe S, Takeda K, Yu ZX, Iwata N, Kajigaya S (2000) Cloning and characterization of a novel adaptor protein, CIN85, that interacts with c-Cbl. Biochem Biophys Res Commun 268(2):321–328

    Article  PubMed  CAS  Google Scholar 

  4. Ma Y, Yang H, Qi J, Liu D, Xiong P, Xu Y et al (2010) CD2AP is indispensable to multistep cytotoxic process by NK cells. Mol Immunol 47(5):1074–1082

    Article  PubMed  CAS  Google Scholar 

  5. Wolf G, Stahl RAK (2003) CD2-associated protein and glomerular disease. Lancet 362(9397):1746–1748

    Article  PubMed  CAS  Google Scholar 

  6. Shih NY, Li J, Cotran R, Mundel P, Miner JH, Shaw AS (2001) CD2AP localizes to the slit diaphragm and binds to nephrin via a novel C-terminal domain. Am J Pathol 159(6):2303–2308

    Article  PubMed  CAS  Google Scholar 

  7. Schwarz K, Simons M, Reiser J, Saleem MA, Faul C, Kriz W et al (2001) Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin. J Clin Invest 108(11):1621–1629

    PubMed  CAS  Google Scholar 

  8. Yuan H, Takeuchi E, Salant DJ (2002) Podocyte slit-diaphragm protein nephrin is linked to the actin cytoskeleton. Am J Physiol Renal Physiol 282(4):F585–F591

    PubMed  CAS  Google Scholar 

  9. Lu C, Ren W, Su X-M, Chen J-Q, Wu S-H, Guo X-R et al (2008) CREB and Sp1 regulate the human CD2AP gene promoter activity in renal tubular epithelial cells. Arch Biochem Biophys 474(1):143–149

    Article  PubMed  CAS  Google Scholar 

  10. Lehtonen S, Zhao F, Lehtonen E (2002) CD2-associated protein directly interacts with the actin cytoskeleton. Am J Physiol Renal Physiol 283(4):F734–F743

    PubMed  Google Scholar 

  11. Huber TB, Kottgen M, Schilling B, Walz G, Benzing T (2001) Interaction with podocin facilitates nephrin signaling. J Biol Chem 276(45):41543–41546

    Article  PubMed  CAS  Google Scholar 

  12. Shih NY, Li J, Karpitskii V, Nguyen A, Dustin ML, Kanagawa O et al (1999) Congenital nephrotic syndrome in mice lacking CD2-associated protein. Science 286(5438):312–315

    Article  PubMed  CAS  Google Scholar 

  13. Löwik MM, Groenen PJTA, Pronk I, Lilien MR, Goldschmeding R, Dijkman HB et al (2007) Focal segmental glomerulosclerosis in a patient homozygous for a CD2AP mutation. Kidney Int 72(10):1198–1203

    Article  PubMed  Google Scholar 

  14. Grunkemeyer JA, Kwoh C, Huber TB, Shaw AS (2005) CD2-associated protein (CD2AP) expression in podocytes rescues lethality of CD2AP deficiency. J Biol Chem 280(33):29677–29681

    Article  PubMed  CAS  Google Scholar 

  15. Kim JM, Wu H, Green G, Winkler CA, Kopp JB, Miner JH et al (2003) CD2-associated protein haploinsufficiency is linked to glomerular disease susceptibility. Science 300(5623):1298–1300

    Article  PubMed  CAS  Google Scholar 

  16. Brett TJ, Traub LM, Fremont DH (2002) Structure 10(6):797–809

    Article  PubMed  CAS  Google Scholar 

  17. Cormont M, Metón I, Mari M, Monzo P, Keslair F, Gaskin C, McGraw TE, Le Marchand-Brustel Y (2003) Traffic 4(2):97–112

    Article  PubMed  CAS  Google Scholar 

  18. Gauthier NC, Monzo P, Gonzalez T, Doye A, Oldani A, Gounon P, Ricci V, Cormont M, Boquet P (2007) J Cell Biol 177(2):343–354

    Article  PubMed  CAS  Google Scholar 

  19. Konishi H, Tashiro K, Murata Y, Nabeshi H, Yamauchi E, Taniguchi H (2006) CFBP is a novel tyrosine-phosphorylated protein that might function as a regulator of CIN85/CD2AP. J Biol Chem 281(39):28919–28931

    Article  PubMed  CAS  Google Scholar 

  20. Lynch DK, Winata SC, Lyons RJ, Hughes WE, Lehrbach GM, Wasinger V et al (2003) A cortactin-CD2-associated protein (CD2AP) complex provides a novel link between epidermal growth factor receptor endocytosis and the actin cytoskeleton. J Biol Chem 278(24):21805–21813

    Article  PubMed  CAS  Google Scholar 

  21. Tossidou I, Niedenthal R, Klaus M, Teng B, Worthmann K, King BL et al (2012) CD2AP regulates SUMOylation of CIN85 in podocytes. Mol Cell Biol 32(6):1068–1079

    Article  PubMed  CAS  Google Scholar 

  22. Calabia-Linares C, Robles-Valero J, de la Fuente H, Perez-Martinez M, Martín-Cofreces N, Alfonso-Pérez M et al (2011) Endosomal clathrin drives actin accumulation at the immunological synapse. J Cell Sci 124(Pt 5):820–830

    Article  PubMed  CAS  Google Scholar 

  23. Huber TB, Hartleben B, Kim J, Schmidts M, Schermer B, Keil A et al (2003) Nephrin and CD2AP associate with phosphoinositide 3-OH kinase and stimulate AKT-dependent signaling. Mol Cell Biol 23(14):4917–4928

    Article  PubMed  CAS  Google Scholar 

  24. Schiffer M, Mundel P, Shaw AS, Böttinger EP (2004) A novel role for the adaptor molecule CD2-associated protein in transforming growth factor-beta-induced apoptosis. J Biol Chem 279(35):37004–37012

    Article  PubMed  CAS  Google Scholar 

  25. Xavier S, Niranjan T, Krick S, Zhang T, Ju W, Shaw AS et al (2009) TbetaRI independently activates Smad- and CD2AP-dependent pathways in podocytes. J Am Soc Nephrol 20(10):2127–2137

    Article  PubMed  CAS  Google Scholar 

  26. Asanuma K, Campbell KN, Kim K, Faul C, Mundel P (2007) Nuclear relocation of the nephrin and CD2AP-binding protein dendrin promotes apoptosis of podocytes. Proc Natl Acad Sci USA 104(24):10134–10139

    Article  PubMed  CAS  Google Scholar 

  27. He F, Chen S, Wang H, Shao N, Tian X, Jiang H et al (2011) Regulation of CD2-associated protein influences podocyte endoplasmic reticulum stress-mediated apoptosis induced by albumin overload. Gene 484(1–2):18–25

    Article  PubMed  CAS  Google Scholar 

  28. He F-F, Zhang C, Chen S, Deng B-Q, Wang H, Shao N et al (2011) Role of CD2-associated protein in albumin overload-induced apoptosis in podocytes. Cell Biol Int 35(8):827–834

    Article  PubMed  CAS  Google Scholar 

  29. Su X-M, Ren W, Lu C, Chen J-Q, Wu S-H, Chen R-H et al (2009) Functional characterization of the regulatory region of human CD2-associated protein promoter in HEK 293 cells. Am J Nephrol 29(3):203–212

    Article  PubMed  CAS  Google Scholar 

  30. Xu H-G, Ren W, Zou L, Wang Y, Jin R, Zhou G-P (2012) Transcriptional control of human CD2AP expression: the role of Sp1 and Sp3. Mol Biol Rep 39(2):1479–1486

    Article  PubMed  CAS  Google Scholar 

  31. Lu C, Ren W, Su X-M, Chen J-Q, Wu S-H, Zhou G-P (2009) EGF-recruited JunD/c-fos complexes activate CD2AP gene promoter and suppress apoptosis in renal tubular epithelial cells. Gene 433(1–2):56–64

    Article  PubMed  CAS  Google Scholar 

  32. Miner JH, Morello R, Andrews KL, Li C, Antignac C, Shaw AS et al (2002) Transcriptional induction of slit diaphragm genes by Lmx1b is required in podocyte differentiation. J Clin Invest 109(8):1065–1072

    PubMed  CAS  Google Scholar 

  33. Naj AC, Jun G, Beecham GW, Wang L-S, Vardarajan BN, Buros J et al (2011) Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer’s disease. Nat Genet 43(5):436–441

    Article  PubMed  CAS  Google Scholar 

  34. Hollingworth P, Harold D, Sims R, Gerrish A, Lambert J-C, Carrasquillo MM et al (2011) Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease. Nat Genet 43(5):429–435

    Article  PubMed  CAS  Google Scholar 

  35. Carrasquillo MM, Belbin O, Hunter TA, Ma L, Bisceglio GD, Zou F et al (2011) Replication of EPHA1 and CD33 associations with late-onset Alzheimer’s disease: a multi-centre case-control study. Mol Neurodegener 6(1):54

    Article  PubMed  CAS  Google Scholar 

  36. Tan L, Yu J-T, Zhang W, Wu Z-C, Zhang Q, Liu Q-Y, et al (2012) Association of GWAS-linked loci with late-onset Alzheimer’s disease in a northern Han Chinese population. Alzheimers Dement

    Google Scholar 

  37. Chung SJ, Lee J-H, Kim SY, You S, Kim MJ, Lee J-Y, et al (2012) Association of GWAS top hits with late-onset Alzheimer disease in Korean population. Alzheimer Dis Assoc Disord

    Google Scholar 

  38. Ovcharenko I, Nobrega MA, Loots GG, Stubbs L (2004) ECR Browser: a tool for visualizing and accessing data from comparisons of multiple vertebrate genomes. Nucleic Acids Res 32(Web Server issue):W280–W286

    Article  PubMed  CAS  Google Scholar 

  39. Ward LD, Kellis M (2012) HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants. Nucleic Acids Res 40(Database issue):D930–D934

    Article  PubMed  CAS  Google Scholar 

  40. Johnson AD, Handsaker RE, Pulit SL, Nizzari MM, O’Donnell CJ, de Bakker PIW (2008) SNAP: a web-based tool for identification and annotation of proxy SNPs using HapMap. Bioinformatics 24(24):2938–2939

    Article  PubMed  CAS  Google Scholar 

  41. Su AI, Wiltshire T, Batalov S, Lapp H, Ching KA, Block D et al (2004) A gene atlas of the mouse and human protein-encoding transcriptomes. Proc Natl Acad Sci USA 101(16):6062–6067

    Article  PubMed  CAS  Google Scholar 

  42. Saito A, Miyauchi N, Hashimoto T, Karasawa T, Han GD, Kayaba M et al (2011) Neurexin-1, a presynaptic adhesion molecule, localizes at the slit diaphragm of the glomerular podocytes in kidneys. Am J Physiol Regul Integr Comp Physiol 300(2):R340–R348

    Article  PubMed  CAS  Google Scholar 

  43. Tsui CC, Pierchala BA (2008) CD2AP and Cbl-3/Cbl-c constitute a critical checkpoint in the regulation of ret signal transduction. J Neurosci 28(35):8789–8800

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Human Genetics, School of Molecular Medical Sciences, Queen’s Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK

    Christopher Medway & Kevin Morgan

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  1. Christopher Medway
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  2. Kevin Morgan
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Correspondence to Christopher Medway .

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Editors and Affiliations

  1. Queen's Medical Centre, School of Molecular Medical Sciences, University of Nottingham, Hucknall Road, Nottingham, NG7 2UH, United Kingdom

    Kevin Morgan

  2. , Department of Neuroscience, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, 32224, USA

    Minerva M. Carrasquillo

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Medway, C., Morgan, K. (2013). CD2-Associated Protein (CD2AP). In: Morgan, K., Carrasquillo, M. (eds) Genetic Variants in Alzheimer's Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7309-1_11

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