The FE65 proteins and Alzheimer's disease

Journal of Neuroscience Research - Tập 86 Số 4 - Trang 744-754 - 2008
Declan M. McLoughlin1,2, Christopher Miller1
1Department of Neuroscience, Institute of Psychiatry, King's College London, MRC Centre for Neurodegeneration Research, London, United Kingdom
2Section of Old Age Psychiatry, Institute of Psychiatry, King's College London, MRC Centre for Neurodegeneration Research, London, United Kingdom

Tóm tắt

AbstractThe FE65s (FE65, FE65L1, and FE65L2) are a family of multidomain adaptor proteins that form multiprotein complexes with a range of functions. FE65 is brain‐enriched, whereas FE65L1 and FE65L2 are more widely expressed. All three members contain a WW domain and two PTB domains. Through the PTB2 domain, they all interact with the Alzheimer's disease amyloid precursor protein (APP) intracellular domain (AICD) and can alter APP processing. After sequential proteolytic processing of membrane‐bound APP and release of AICD to the cytoplasm, FE65 can translocate to the nucleus to participate in gene transcription events. This role is further mediated by interactions of FE65 PTB1 with the transcription factors CP2/LSF/LBP1 and Tip60 and the WW domain with the nucleosome assembly factor SET. However, FE65 target genes have not yet been confirmed. The FE65 PTB1 domain also interacts with two cell surface lipoproteins receptors, the low‐density lipoprotein receptor‐related protein (LRP) and ApoEr2, forming trimeric complexes with APP. The FE55 WW domain also binds to mena, through which it functions in regulation of the actin cytoskeleton, cell motility, and neuronal growth cone formation. While single knockout mice appear normal, double FE65−/−/FE65L1−/− mice have substantial neurodevelopmental defects. These include heterotopic neurons and axonal pathfinding defects, findings similar to findings in both Mena and triple APP:APLP1:APLP2 knockout mice and also lissencephalopathies in humans. Thus APPs, FE65s, and mena may act together in a developmental signalling pathway. This article reviews the known functions of the FE65 family and their role in APP function and Alzheimer's disease. © 2007 Wiley‐Liss, Inc.

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Tài liệu tham khảo

10.1177/0957154X9100200505

10.1074/jbc.M104059200

10.1074/jbc.M401925200

10.1016/S0092-8674(02)00809-7

10.1523/JNEUROSCI.22-17-07340.2002

10.1111/j.1460-9568.2004.03611.x

10.1007/s003359900800

10.1128/MCB.16.11.6229

10.1038/nrm2009

10.1093/hmg/5.10.1589

10.1074/jbc.M205227200

10.1126/science.1058783

10.1074/jbc.M402248200

10.1128/MCB.02393-05

10.1074/jbc.M309561200

10.1046/j.1471-4159.2001.00516.x

10.1093/nar/19.19.5269

10.1042/bj3300513

10.1074/jbc.272.52.32869

10.1159/000111865

10.1016/S0140-6736(05)67889-0

10.1074/jbc.270.52.30853

10.1096/fj.04-3395com

10.1073/pnas.261463298

10.1073/pnas.93.20.10832

10.1046/j.1471-4159.2002.01009.x

10.1038/sj.emboj.7600926

10.1016/j.neuron.2006.09.016

10.1074/jbc.M502861200

10.1038/sj.embor.7400704

10.1038/sj.emboj.7600390

10.1038/nrn2009

10.1074/jbc.M600728200

10.1074/jbc.M411855200

10.1002/jnr.20408

10.1016/S0306-4522(02)00422-0

Kim HS, 2003, C‐terminal fragments of amyloid precursor protein exert neurotoxicity by inducing glycogen synthase kinase‐3β expression, FASEB J, 17, U253

10.1074/jbc.C100447200

10.1523/JNEUROSCI.4883-04.2005

10.1016/j.expneurol.2003.10.011

10.1523/JNEUROSCI.21-21-08354.2001

10.1046/j.1471-4159.2002.01016.x

10.1074/jbc.M306403200

10.1523/JNEUROSCI.2766-05.2005

10.1074/jbc.M006274200

10.1016/S0896-6273(00)81092-2

10.1097/00001756-200011090-00041

10.1074/jbc.M300503200

10.1074/jbc.M405602200

10.1074/jbc.M310001200

10.1136/jnnp.72.2.152

10.1016/S0960-9822(00)00246-3

10.1073/pnas.0600549103

10.1074/jbc.M507735200

10.1016/S0014-5793(96)01128-3

10.1016/j.tins.2006.03.001

10.1074/jbc.M007340200

10.1093/hmg/ddh054

10.1111/j.1365-2443.2006.00968.x

10.1016/S0896-6273(03)00810-9

10.1016/j.neuron.2005.04.008

10.1074/jbc.M311479200

10.1523/JNEUROSCI.5451-03.2004

10.1038/sj.emboj.7600860

10.1016/j.brainresrev.2006.04.005

10.1146/annurev.neuro.24.1.1041

10.1074/jbc.274.12.7952

10.1083/jcb.153.7.1403

10.1523/JNEUROSCI.23-13-05407.2003

10.1111/j.1471-4159.2005.03026.x

10.1074/jbc.M208110200

10.1073/pnas.0437908100

10.1016/j.mcn.2003.07.002

10.1016/j.bbadis.2004.06.017

10.1016/S0014-5793(01)02122-6

10.1074/jbc.M504278200

10.1006/bbrc.1999.0639

10.1016/S0304-3940(98)00995-1

10.1042/bj20020562

10.1038/sj.embor.7400309

10.1074/jbc.273.50.33556

10.1016/j.molmed.2005.08.004

10.1186/1750-1326-1-4

10.1242/jcs.01323

10.1016/j.neuron.2004.09.010

10.1021/bi027375c

10.1002/jnr.10834

10.1074/jbc.M311652200

World Health Organization, 2000, The World Health Report 2000—health systems: improving performance

10.1074/jbc.M508445200

10.1074/jbc.273.32.20128

10.1074/jbc.M100792200

Zambrano N, 2002, feh‐1 And apl‐1, the Caenorhabditis elegans orthologues of mammalian Fe65 and β‐amyloid precursor protein genes, are involved in the same pathway that controls nematode pharyngeal pumping, J Cell Sci, 115, 1411, 10.1242/jcs.115.7.1411

10.1021/bi027117f

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Journal of Neuroscience Research

Tập 86 Số 4

744-754

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