Sorting of Alzheimer Disease Amyloid
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[email protected] Sorting of the Alzheimer's Disease Amyloid Precursor Protein Mediated by the AP-4 Complex Burgos PV, Mardones GA, Rojas AL, daSilva LL, Prabhu Y, Hurley JH, Bonifacino JS. Dev Cell. 2010 Mar 16;18(3):425-36.
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Transcript of Sorting of Alzheimer Disease Amyloid
Sorting of the Alzheimer's Disease Amyloid Precursor Protein Mediated
by the AP-4 Complex
Burgos PV, Mardones GA, Rojas AL, daSilva LL, Prabhu Y, Hurley JH, Bonifacino JS.Dev Cell. 2010 Mar 16;18(3):425-36.
M.Boehm, R.C.Aguilar and J.S.BonifacinoThe EMBO Journal Vol. 20 No. 22 pp. 6265±6276, 2001
Zhang Therapeutic Targeting of the Alpha-Secretase Pathway to Treat Alzheimer’s Diseasehttp://www.discoverymedicine.com/Can-Zhang/2009/07/29/therapeutic-targeting-of-the-alpha-secretase-pathway-to-treat-alzheimers-disease/
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The FASEB Journal October 1, 2003 vol. 17 no. 13 1951-1953
Highlights
A sorting signal in the cytosolic tail of APP interacts with the μ4 subunit of AP-4X-ray crystallography reveals that the APP signal binds to a distinct site on μ4Disruption of the APP-AP-4 interaction decreases APP localization to endosomesRedistribution of APP enhances γ-secretase-mediated cleavage to amyloid-β peptide
Fig. 2. Crystal structure of the μ4 C-terminal domain in complex with a peptide signal from APP.
Fig. 4. Redistribution of APP from Endosomes to the TGN upon Disruption of Its Interaction with μ4
YKAAA
m4 RNAi
Fig. 5. Disruption of the APP-μ4 interaction alters CTF levels and p3/ Aβ secretion.
Fig. 7. Altered processing of CTFβ upon disruption of the YKFFE-μ4 interaction. Experiments were performed as in Fig. 6, with the variations indicated below. The positions of molecular mass markers and different APP species are indicated.
1. Adaptor protein complex-4 (AP-4) deficiency causes a novel autosomal recessive cerebral palsy syndrome with microcephaly and intellectual disability. Moreno-De-Luca A, Helmers SL, Mao H, et al. JOURNAL OF MEDICAL GENETICS Volume: 48 Issue: 2 Pages: 141-144 Published: FEB 20112. Bidirectional transport between the trans-Golgi network and the endosomal system. Anitei M, Wassmer T, Stange C, et al. MOLECULAR MEMBRANE BIOLOGY Volume: 27 Issue: 8 Pages: 443-456 Published: NOV 20103. Ang2/Fat-Free Is a Conserved Subunit of the Golgi-associated Retrograde Protein Complex. Perez-Victoria FJ, Schindler C, Magadan JG, et al. MOLECULAR BIOLOGY OF THE CELL Volume: 21 Issue: 19 Pages: 3386-3395 Published: OCT 1 2010Times Cited: 34. Vesicle Transport: A New Player in APP Trafficking. Owen DJ, Collins BMCURRENT BIOLOGY Volume: 20 Issue: 9 Pages: R413-R415 Published: MAY 11 2010
