| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 47, 45013-45019, November 22, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Center for Basic Neuroscience and Department of Cell
Biology, University of Texas Southwestern Medical Center, Dallas,
Texas 75390
Presenilin and nicastrin are essential components
of the
Mammalian APH-1 Interacts with Presenilin and Nicastrin and Is
Required for Intramembrane Proteolysis of Amyloid-
Precursor Protein
and Notch*
,,,
-secretase complex that is required for the intramembrane
proteolysis of an increasing number of membrane proteins including the
amyloid-
precursor protein (APP) and Notch. By using
co-immunoprecipitation and nickel affinity pull-down approaches, we now
show that mammalian APH-1 (mAPH-1), a conserved multipass membrane
protein, physically associates with nicastrin and the heterodimers of
the presenilin amino- and carboxyl-terminal fragments in human cell
lines and in rat brain. Similar to the loss of presenilin
or nicastrin, the inactivation of endogenous
mAPH-1 using small interfering RNAs results in the decrease
of presenilin levels, accumulation of -secretase substrates (APP
carboxyl-terminal fragments), and reduction of -secretase products
(amyloid- peptides and the intracellular domains of APP and Notch).
These data indicate that mAPH-1 is probably a functional component of
the -secretase complex required for the intramembrane proteolysis of
APP and Notch.
*
This work was supported by the UT Southwestern
Endowed Scholars Program for Biomedical Research and the UT
Southwestern Alzheimer Disease Center Pilot Grant 35279.The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
These authors contributed equally to this work.
§
Thomas Hicks Scholar in Biomedical Research. To whom correspondence
should be addressed: Center for Basic Neuroscience, University of Texas
Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX
75390-9111. Tel.: 214-648-5157; Fax: 214-648-1801; E-mail:
Gang.Yu@UTSouthwestern.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  W. S. Liang, T. Dunckley, T. G. Beach, A. Grover, D. Mastroeni, K. Ramsey, R. J. Caselli, W. A. Kukull, D. McKeel, J. C. Morris, et al. Altered neuronal gene expression in brain regions differentially affected by Alzheimer's disease: a reference data set Physiol Genomics, April 1, 2008; 33(2): 240 - 256. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Dunys, T. Kawarai, J. Sevalle, V. Dolcini, P. St. George-Hyslop, C. A. Da Costa, and F. Checler p53-dependent Aph-1 and Pen-2 Anti-apoptotic Phenotype Requires the Integrity of the {gamma}-Secretase Complex but Is Independent of Its Activity J. Biol. Chem., April 6, 2007; 282(14): 10516 - 10525. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Haleem, C. F. Lippa, T. W. Smith, H. Kowa, Jianlin Wu, and T. Iwatsubo Presenilin-1 C410Y Alzheimer Disease Plaques Contain Synaptic Proteins American Journal of Alzheimer's Disease and Other Dementias, April 1, 2007; 22(2): 137 - 144. [Abstract] [PDF]
|
|
|
|
|
|
A. Kern, B. Roempp, K. Prager, J. Walter, and C. Behl Down-regulation of Endogenous Amyloid Precursor Protein Processing due to Cellular Aging J. Biol. Chem., February 3, 2006; 281(5): 2405 - 2413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Laudon, E. M. Hansson, K. Melen, A. Bergman, M. R. Farmery, B. Winblad, U. Lendahl, G. von Heijne, and J. Naslund A Nine-transmembrane Domain Topology for Presenilin 1 J. Biol. Chem., October 21, 2005; 280(42): 35352 - 35360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kim, H. Ki, H.-S. Park, and K. Kim Presenilin-1 D257A and D385A Mutants Fail to Cleave Notch in Their Endoproteolyzed Forms, but Only Presenilin-1 D385A Mutant Can Restore Its {gamma}-Secretase Activity with the Compensatory Overexpression of Normal C-terminal Fragment J. Biol. Chem., June 10, 2005; 280(23): 22462 - 22472. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Zhou, H. Zhou, P. J. Walian, and B. K. Jap CD147 is a regulatory subunit of the {gamma}-secretase complex in Alzheimer's disease amyloid {beta}-peptide production PNAS, May 24, 2005; 102(21): 7499 - 7504. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-w. Zhang, W.-j. Luo, H. Wang, P. Lin, K. S. Vetrivel, F. Liao, F. Li, P. C. Wong, M. G. Farquhar, G. Thinakaran, et al. Nicastrin Is Critical for Stability and Trafficking but Not Association of Other Presenilin/{gamma}-Secretase Components J. Biol. Chem., April 29, 2005; 280(17): 17020 - 17026. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. J. Wrigley, I. Schurov, E. J. Nunn, A. C. L. Martin, E. E. Clarke, S. Ellis, T. P. Bonnert, M. S. Shearman, and D. Beher Functional Overexpression of {gamma}-Secretase Reveals Protease-independent Trafficking Functions and a Critical Role of Lipids for Protease Activity J. Biol. Chem., April 1, 2005; 280(13): 12523 - 12535. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Niimura, N. Isoo, N. Takasugi, M. Tsuruoka, K. Ui-Tei, K. Saigo, Y. Morohashi, T. Tomita, and T. Iwatsubo Aph-1 Contributes to the Stabilization and Trafficking of the {gamma}-Secretase Complex through Mechanisms Involving Intermolecular and Intramolecular Interactions J. Biol. Chem., April 1, 2005; 280(13): 12967 - 12975. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Ma, T. Li, D. L. Price, and P. C. Wong APH-1a Is the Principal Mammalian APH-1 Isoform Present in {gamma}-Secretase Complexes during Embryonic Development J. Neurosci., January 5, 2005; 25(1): 192 - 198. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Hansson, S. Frykman, M. R. Farmery, L. O. Tjernberg, C. Nilsberth, S. E. Pursglove, A. Ito, B. Winblad, R. F. Cowburn, J. Thyberg, et al. Nicastrin, Presenilin, APH-1, and PEN-2 Form Active {gamma}-Secretase Complexes in Mitochondria J. Biol. Chem., December 3, 2004; 279(49): 51654 - 51660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-H. Kim, Y. I. Yin, Y.-M. Li, and S. S. Sisodia Evidence That Assembly of an Active {gamma}-Secretase Complex Occurs in the Early Compartments of the Secretory Pathway J. Biol. Chem., November 19, 2004; 279(47): 48615 - 48619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bergman, H. Laudon, B. Winblad, J. Lundkvist, and J. Naslund The Extreme C Terminus of Presenilin 1 Is Essential for {gamma}-Secretase Complex Assembly and Activity J. Biol. Chem., October 29, 2004; 279(44): 45564 - 45572. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. S. Vetrivel, H. Cheng, W. Lin, T. Sakurai, T. Li, N. Nukina, P. C. Wong, H. Xu, and G. Thinakaran Association of {gamma}-Secretase with Lipid Rafts in Post-Golgi and Endosome Membranes J. Biol. Chem., October 22, 2004; 279(43): 44945 - 44954. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Shirotani, D. Edbauer, S. Prokop, C. Haass, and H. Steiner Identification of Distinct {gamma}-Secretase Complexes with Different APH-1 Variants J. Biol. Chem., October 1, 2004; 279(40): 41340 - 41345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wang, W.-j. Luo, Y.-w. Zhang, Y.-M. Li, G. Thinakaran, P. Greengard, and H. Xu Presenilins and {gamma}-Secretase Inhibitors Affect Intracellular Trafficking and Cell Surface Localization of the {gamma}-Secretase Complex Components J. Biol. Chem., September 24, 2004; 279(39): 40560 - 40566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Edbauer, C. Kaether, H. Steiner, and C. Haass Co-expression of Nicastrin and Presenilin Rescues a Loss of Function Mutant of APH-1 J. Biol. Chem., September 3, 2004; 279(36): 37311 - 37315. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Xie, D. M. Romano, D. M. Kovacs, and R. E. Tanzi Effects of RNA Interference-mediated Silencing of {gamma}-Secretase Complex Components on Cell Sensitivity to Caspase-3 Activation J. Biol. Chem., August 13, 2004; 279(33): 34130 - 34137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Prokop, K. Shirotani, D. Edbauer, C. Haass, and H. Steiner Requirement of PEN-2 for Stabilization of the Presenilin N-/C-terminal Fragment Heterodimer within the {gamma}-Secretase Complex J. Biol. Chem., May 28, 2004; 279(22): 23255 - 23261. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bergman, E. M. Hansson, S. E. Pursglove, M. R. Farmery, L. Lannfelt, U. Lendahl, J. Lundkvist, and J. Naslund Pen-2 Is Sequestered in the Endoplasmic Reticulum and Subjected to Ubiquitylation and Proteasome-mediated Degradation in the Absence of Presenilin J. Biol. Chem., April 16, 2004; 279(16): 16744 - 16753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-F. Lee, S. Shah, C. Yu, W. C. Wigley, H. Li, M. Lim, K. Pedersen, W. Han, P. Thomas, J. Lundkvist, et al. A Conserved GXXXG Motif in APH-1 Is Critical for Assembly and Activity of the {gamma}-Secretase Complex J. Biol. Chem., February 6, 2004; 279(6): 4144 - 4152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. R. Fortna, A. S. Crystal, V. A. Morais, D. S. Pijak, V. M.-Y. Lee, and R. W. Doms Membrane Topology and Nicastrin-enhanced Endoproteolysis of APH-1, a Component of the {gamma}-Secretase Complex J. Biol. Chem., January 30, 2004; 279(5): 3685 - 3693. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Jankowsky, D. J. Fadale, J. Anderson, G. M. Xu, V. Gonzales, N. A. Jenkins, N. G. Copeland, M. K. Lee, L. H. Younkin, S. L. Wagner, et al. Mutant presenilins specifically elevate the levels of the 42 residue {beta}-amyloid peptide in vivo: evidence for augmentation of a 42-specific {gamma} secretase Hum. Mol. Genet., January 15, 2004; 13(2): 159 - 170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Milhavet, D. S. Gary, and M. P. Mattson RNA Interference in Biology and Medicine Pharmacol. Rev., December 1, 2003; 55(4): 629 - 648. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Aguzzi and C. Haass Games Played by Rogue Proteins in Prion Disorders and Alzheimer's Disease Science, October 31, 2003; 302(5646): 814 - 818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. A. Morais, A. S. Crystal, D. S. Pijak, D. Carlin, J. Costa, V. M.-Y. Lee, and R. W. Doms The Transmembrane Domain Region of Nicastrin Mediates Direct Interactions with APH-1 and the {gamma}-Secretase Complex J. Biol. Chem., October 31, 2003; 278(44): 43284 - 43291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Guo, E. J. Hong, J. Fernandes, S. L. Zipursky, and B. A. Hay A reporter for amyloid precursor protein {gamma}-secretase activity in Drosophila Hum. Mol. Genet., October 16, 2003; 12(20): 2669 - 2678. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-H. Kim, T. Ikeuchi, C. Yu, and S. S. Sisodia Regulated Hyperaccumulation of Presenilin-1 and the "{gamma}-Secretase" Complex: EVIDENCE FOR DIFFERENTIAL INTRAMEMBRANOUS PROCESSING OF TRANSMEMBRANE SUBSTRATES J. Biol. Chem., September 5, 2003; 278(36): 33992 - 34002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Weggen, J. L. Eriksen, S. A. Sagi, C. U. Pietrzik, Todd. E. Golde, and E. H. Koo A{beta}42-lowering Nonsteroidal Anti-inflammatory Drugs Preserve Intramembrane Cleavage of the Amyloid Precursor Protein (APP) and ErbB-4 Receptor and Signaling through the APP Intracellular Domain J. Biol. Chem., August 15, 2003; 278(33): 30748 - 30754. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Tian, S. V. Ghanekar, D. Aharony, A. B. Shenvi, R. T. Jacobs, X. Liu, and B. D. Greenberg The Mechanism of {gamma}-Secretase: MULTIPLE INHIBITOR BINDING SITES FOR TRANSITION STATE ANALOGS AND SMALL MOLECULE INHIBITORS J. Biol. Chem., August 1, 2003; 278(31): 28968 - 28975. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Marques, U. Keil, A. Bonert, B. Steiner, C. Haass, W. E. Muller, and A. Eckert Neurotoxic Mechanisms Caused by the Alzheimer's Disease-linked Swedish Amyloid Precursor Protein Mutation: OXIDATIVE STRESS, CASPASES, AND THE JNK PATHWAY J. Biol. Chem., July 18, 2003; 278(30): 28294 - 28302. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Xia and M. S. Wolfe Intramembrane proteolysis by presenilin and presenilin-like proteases J. Cell Sci., July 15, 2003; 116(14): 2839 - 2844. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. Pasternak, R. D. Bagshaw, M. Guiral, S. Zhang, C. A. Ackerley, B. J. Pak, J. W. Callahan, and D. J. Mahuran Presenilin-1, Nicastrin, Amyloid Precursor Protein, and {gamma}-Secretase Activity Are Co-localized in the Lysosomal Membrane J. Biol. Chem., July 11, 2003; 278(29): 26687 - 26694. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Farmery, L. O. Tjernberg, S. E. Pursglove, A. Bergman, B. Winblad, and J. Naslund Partial Purification and Characterization of {gamma}-Secretase from Post-mortem Human Brain J. Biol. Chem., June 27, 2003; 278(27): 24277 - 24284. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Sato, N. Dohmae, Y. Qi, N. Kakuda, H. Misonou, R. Mitsumori, H. Maruyama, E. H. Koo, C. Haass, K. Takio, et al. Potential Link between Amyloid {beta}-Protein 42 and C-terminal Fragment {gamma} 49-99 of {beta}-Amyloid Precursor Protein J. Biol. Chem., June 27, 2003; 278(27): 24294 - 24301. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Hu and M. E. Fortini Different cofactor activities in {gamma}-secretase assembly: evidence for a nicastrin-Aph-1 subcomplex J. Cell Biol., May 26, 2003; 161(4): 685 - 690. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Crystal, V. A. Morais, T. C. Pierson, D. S. Pijak, D. Carlin, V. M.-Y. Lee, and R. W. Doms Membrane Topology of {gamma}-Secretase Component PEN-2 J. Biol. Chem., May 23, 2003; 278(22): 20117 - 20123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Shirotani, D. Edbauer, A. Capell, J. Schmitz, H. Steiner, and C. Haass gamma -Secretase Activity Is Associated with a Conformational Change of Nicastrin J. Biol. Chem., May 2, 2003; 278(19): 16474 - 16477. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Li, G. Ma, H. Cai, D. L. Price, and P. C. Wong Nicastrin Is Required for Assembly of Presenilin/gamma -Secretase Complexes to Mediate Notch Signaling and for Processing and Trafficking of beta -Amyloid Precursor Protein in Mammals J. Neurosci., April 15, 2003; 23(8): 3272 - 3277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. S. Grimm, D. Beher, S. F. Lichtenthaler, M. S. Shearman, K. Beyreuther, and T. Hartmann gamma -Secretase Cleavage Site Specificity Differs for Intracellular and Secretory Amyloid beta J. Biol. Chem., April 4, 2003; 278(15): 13077 - 13085. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Wolfe {gamma}-Secretase--Intramembrane Protease with a Complex Sci. Aging Knowl. Environ., March 19, 2003; 2003(11): pe7 - 7. [Abstract] [Full Text]
|
|
|
|
 |
|
 T. E. Golde and C. B. Eckman Physiologic and Pathologic Events Mediated by Intramembranous and Juxtamembranous Proteolysis Sci. Signal., March 4, 2003; 2003(172): re4 - re4. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-j. Luo, H. Wang, H. Li, B. S. Kim, S. Shah, H.-J. Lee, G. Thinakaran, T.-W. Kim, G. Yu, and H. Xu PEN-2 and APH-1 Coordinately Regulate Proteolytic Processing of Presenilin 1 J. Biol. Chem., February 28, 2003; 278(10): 7850 - 7854. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Fluhrer, G. Multhaup, A. Schlicksupp, M. Okochi, M. Takeda, S. Lammich, M. Willem, G. Westmeyer, W. Bode, J. Walter, et al. Identification of a beta -Secretase Activity, Which Truncates Amyloid beta -Peptide after Its Presenilin-dependent Generation J. Biol. Chem., February 14, 2003; 278(8): 5531 - 5538. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
