 |
||||
|
||||
|
||||
|
||||
.gif?ad=17923&adview=true)
Previous Article | Next Article
Volume 17, Number 6, Issue of March 15, 1997 pp. 1971-1980
Copyright ©1997 Society for NeuroscienceLight and Electron Microscopic Localization of Presenilin-1 in Primate Brain
Received Oct. 29, 1996; revised Jan. 9, 1997; accepted Jan. 13, 1997.
James J. Lah, Craig J. Heilman, Norman R. Nash, Howard D. Rees, Hong Yi, Scott E. Counts, and Allan I. Levey Department of Neurology, Emory University School of Medicine, Atlanta, Georgia 30322
Several genes have been implicated in the pathogenesis of early-onset familial Alzheimer's disease. A majority of the autosomal dominant cases are linked to recently identified mutations in the presenilin-1 gene on chromosome 14. The native presenilin-1 protein in primates has not been well characterized, and its precise localization is unknown. We have studied the native presenilin-1 protein in monkey brain and peripheral tissues by using a monoclonal antibody specific for the N-terminal domain of human presenilin-1. Western blots detect polypeptide species of ~49 and ~32 kDa from COS-7 and PC12 cells transfected with full-length human presenilin-1 cDNA and from in vitro translations of the normal human presenilin-1 mRNA. A 32 kDa polypeptide is detected in monkey peripheral tissues, with the highest expression in testis and lung. In all brain regions the 32 kDa band is the predominant form of presenilin-1, and it is found in particulate subfractions. Light microscopic immunocytochemistry reveals presenilin-1 staining in all brain regions, with the strongest labeling in neurons and neuropil. In addition, weaker immunoreactivity is also present in glia and blood vessels. Neuronal staining shows significant variability, with particularly intense labeling of certain cell types, including large neocortical and hippocampal pyramidal neurons, magnocellular basal forebrain neurons, brainstem motoneurons, and some populations of interneurons. By electron microscopic immunocytochemistry, highly selective presenilin-1 staining is seen on the cytoplasmic surfaces of membranous organelles, which suggest localization to the endoplasmic reticulum-Golgi intermediate compartment, a subdomain of the endoplasmic reticulum, and some coated transport vesicles.
Key words: presenilin; Alzheimer's disease; immunocytochemistry; electron microscopy; endoplasmic reticulum; intermediate compartment; transport vesicles; coated vesicles; monoclonal antibody
This article has been cited by other articles:
V. Dror, T. B. Kalynyak, Y. Bychkivska, M. H. Z. Frey, M. Tee, K. D. Jeffrey, V. Nguyen, D. S. Luciani, and J. D. Johnson
Glucose and Endoplasmic Reticulum Calcium Channels Regulate HIF-1{beta} via Presenilin in Pancreatic {beta}-Cells
J. Biol. Chem., April 11, 2008; 283(15): 9909 - 9916.
[Abstract] [Full Text] [PDF]
J. Chen, A. Zacharek, A. Li, X. Cui, C. Roberts, M. Lu, and M. Chopp
Atorvastatin Promotes Presenilin-1 Expression and Notch1 Activity and Increases Neural Progenitor Cell Proliferation After Stroke
Stroke, January 1, 2008; 39(1): 220 - 226.
[Abstract] [Full Text] [PDF]
M. Zhang, A. Haapasalo, D. Y. Kim, L. A. M. Ingano, W. H. Pettingell, and D. M. Kovacs
Presenilin/{gamma}-secretase activity regulates protein clearance from the endocytic recycling compartment
FASEB J, June 1, 2006; 20(8): 1176 - 1178.
[Abstract] [Full Text] [PDF]
C. G. Almeida, R. H. Takahashi, and G. K. Gouras
Beta-amyloid accumulation impairs multivesicular body sorting by inhibiting the ubiquitin-proteasome system.
J. Neurosci., April 19, 2006; 26(16): 4277 - 4288.
[Abstract] [Full Text] [PDF]
M. Wines-Samuelson and J. Shen
Presenilins in the Developing, Adult, and Aging Cerebral Cortex
Neuroscientist, October 1, 2005; 11(5): 441 - 451.
[Abstract] [PDF]
N. L. Chevallier, S. Soriano, D. E. Kang, E. Masliah, G. Hu, and E. H. Koo
Perturbed Neurogenesis in the Adult Hippocampus Associated with Presenilin-1 A246E Mutation
Am. J. Pathol., July 1, 2005; 167(1): 151 - 159.
[Abstract] [Full Text] [PDF]
M. Khvotchev and T. C. Sudhof
Proteolytic Processing of Amyloid-{beta} Precursor Protein by Secretases Does Not Require Cell Surface Transport
J. Biol. Chem., November 5, 2004; 279(45): 47101 - 47108.
[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]
Z. Zou, B. Chung, T. Nguyen, S. Mentone, B. Thomson, and D. Biemesderfer
Linking Receptor-mediated Endocytosis and Cell Signaling: EVIDENCE FOR REGULATED INTRAMEMBRANE PROTEOLYSIS OF MEGALIN IN PROXIMAL TUBULE
J. Biol. Chem., August 13, 2004; 279(33): 34302 - 34310.
[Abstract] [Full Text] [PDF]
O. M. Grbovic, P. M. Mathews, Y. Jiang, S. D. Schmidt, R. Dinakar, N. B. Summers-Terio, B. P. Ceresa, R. A. Nixon, and A. M. Cataldo
Rab5-stimulated Up-regulation of the Endocytic Pathway Increases Intracellular {beta}-Cleaved Amyloid Precursor Protein Carboxyl-terminal Fragment Levels and A{beta} Production
J. Biol. Chem., August 15, 2003; 278(33): 31261 - 31268.
[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]
E. L. Meyer, N. Strutz, L. C. Gahring, and S. W. Rogers
Glutamate Receptor Subunit 3 Is Modified by Site-specific Limited Proteolysis Including Cleavage by {gamma}-Secretase
J. Biol. Chem., June 20, 2003; 278(26): 23786 - 23796.
[Abstract] [Full Text] [PDF]
G. Pigino, G. Morfini, A. Pelsman, M. P. Mattson, S. T. Brady, and J. Busciglio
Alzheimer's Presenilin 1 Mutations Impair Kinesin-Based Axonal Transport
J. Neurosci., June 1, 2003; 23(11): 4499 - 4508.
[Abstract] [Full Text] [PDF]
A. Herreman, G. Van Gassen, M. Bentahir, O. Nyabi, K. Craessaerts, U. Mueller, W. Annaert, and B. De Strooper
{gamma}-Secretase activity requires the presenilin-dependent trafficking of nicastrin through the Golgi apparatus but not its complex glycosylation
J. Cell Sci., March 15, 2003; 116(6): 1127 - 1136.
[Abstract] [Full Text] [PDF]
S.-H. Kim, J. Y. Leem, J. J. Lah, H. H. Slunt, A. I. Levey, G. Thinakaran, and S. S. Sisodia
Multiple Effects of Aspartate Mutant Presenilin 1 on the Processing and Trafficking of Amyloid Precursor Protein
J. Biol. Chem., November 9, 2001; 276(46): 43343 - 43350.
[Abstract] [Full Text] [PDF]
O. Tarabal, J. Caldero, J. Llado, R. W. Oppenheim, and J. E. Esquerda
Long-Lasting Aberrant Tubulovesicular Membrane Inclusions Accumulate in Developing Motoneurons after a Sublethal Excitotoxic Insult: A Possible Model for Neuronal Pathology in Neurodegenerative Disease
J. Neurosci., October 15, 2001; 21(20): 8072 - 8081.
[Abstract] [Full Text] [PDF]
D. J. Selkoe
Alzheimer's Disease: Genes, Proteins, and Therapy
Physiol Rev, April 1, 2001; 81(2): 741 - 766.
[Abstract] [Full Text] [PDF]
G. Pigino, A. Pelsman, H. Mori, and J. Busciglio
Presenilin-1 Mutations Reduce Cytoskeletal Association, Deregulate Neurite Growth, and Potentiate Neuronal Dystrophy and Tau Phosphorylation
J. Neurosci., February 1, 2001; 21(3): 834 - 842.
[Abstract] [Full Text] [PDF]
R. Siman, A. G. Reaume, M. J. Savage, S. Trusko, Y.-G. Lin, R. W. Scott, and D. G. Flood
Presenilin-1 P264L Knock-In Mutation: Differential Effects on Abeta Production, Amyloid Deposition, and Neuronal Vulnerability
J. Neurosci., December 1, 2000; 20(23): 8717 - 8726.
[Abstract] [Full Text] [PDF]
M. Grilli, E. Diodato, G. Lozza, R. Brusa, M. Casarini, D. Uberti, R. Rozmahel, D. Westaway, P. St George-Hyslop, M. Memo, et al.
Presenilin-1 regulates the neuronal threshold to excitotoxicity both physiologically and pathologically
PNAS, November 7, 2000; 97(23): 12822 - 12827.
[Abstract] [Full Text] [PDF]
H. Tanahashi and T. Tabira
Alzheimer's disease-associated presenilin 2 interacts with DRAL, an LIM-domain protein
Hum. Mol. Genet., September 1, 2000; 9(15): 2281 - 2289.
[Abstract] [Full Text] [PDF]
W. Xia, W. J. Ray, B. L. Ostaszewski, T. Rahmati, W. T. Kimberly, M. S. Wolfe, J. Zhang, A. M. Goate, and D. J. Selkoe
Presenilin complexes with the C-terminal fragments of amyloid precursor protein at the sites of amyloid beta -protein generation
PNAS, August 1, 2000; 97(16): 9299 - 9304.
[Abstract] [Full Text] [PDF]
M. P. Mattson, H. Zhu, J. Yu, and M. S. Kindy
Presenilin-1 Mutation Increases Neuronal Vulnerability to Focal Ischemia In Vivo and to Hypoxia and Glucose Deprivation in Cell Culture: Involvement of Perturbed Calcium Homeostasis
J. Neurosci., February 15, 2000; 20(4): 1358 - 1364.
[Abstract] [Full Text] [PDF]
H. Hauri, F Kappeler, H Andersson, and C Appenzeller
ERGIC-53 and traffic in the secretory pathway
J. Cell Sci., January 2, 2000; 113(4): 587 - 596.
[Abstract] [PDF]
W. J. Ray, M. Yao, J. Mumm, E. H. Schroeter, P. Saftig, M. Wolfe, D. J. Selkoe, R. Kopan, and A. M. Goate
Cell Surface Presenilin-1 Participates in the gamma -Secretase-like Proteolysis of Notch
J. Biol. Chem., December 17, 1999; 274(51): 36801 - 36807.
[Abstract] [Full Text] [PDF]
C. Haass and B. D. Strooper
The Presenilins in Alzheimer's Disease--Proteolysis Holds the Key
Science, October 29, 1999; 286(5441): 916 - 919.
[Abstract] [Full Text]
W. G. Annaert, L. Levesque, K. Craessaerts, I. Dierinck, G. Snellings, D. Westaway, P. St. George-Hyslop, B. Cordell, P. Fraser, and B. De Strooper
Presenilin 1 Controls {gamma}-Secretase Processing of Amyloid Precursor Protein in Pre-Golgi Compartments of Hippocampal Neurons
J. Cell Biol., October 18, 1999; 147(2): 277 - 294.
[Abstract] [Full Text] [PDF]
I. Imafuku, T. Masaki, M. Waragai, S. Takeuchi, M. Kawabata, S.-i. Hirai, S. Ohno, L.E. Nee, C.F. Lippa, I. Kanazawa, et al.
Presenilin 1 Suppresses the Function of c-Jun Homodimers via Interaction with QM/Jif-1
J. Cell Biol., October 4, 1999; 147(1): 121 - 134.
[Abstract] [Full Text] [PDF]
M. Pastorcic and H. K. Das
An Upstream Element Containing an ETS Binding Site Is Crucial for Transcription of the Human Presenilin-1 Gene
J. Biol. Chem., August 20, 1999; 274(34): 24297 - 24307.
[Abstract] [Full Text] [PDF]
T. Nakai, A. Yamasaki, M. Sakaguchi, K. Kosaka, K. Mihara, Y. Amaya, and S. Miura
Membrane Topology of Alzheimer's Disease-related Presenilin 1. EVIDENCE FOR THE EXISTENCE OF A MOLECULAR SPECIES WITH A SEVEN MEMBRANE-SPANNING AND ONE MEMBRANE-EMBEDDED STRUCTURE
J. Biol. Chem., August 13, 1999; 274(33): 23647 - 23658.
[Abstract] [Full Text] [PDF]
A. L. Schwarzman, N. Singh, M. Tsiper, L. Gregori, A. Dranovsky, M. P. Vitek, C. G. Glabe, P. H. St. George-Hyslop, and D. Goldgaber
Endogenous presenilin 1 redistributes to the surface of lamellipodia upon adhesion of Jurkat cells to a collagen matrix
PNAS, July 6, 1999; 96(14): 7932 - 7937.
[Abstract] [Full Text] [PDF]
C. C. Weihl, G. D. Ghadge, S. G. Kennedy, N. Hay, R. J. Miller, and R. P. Roos
Mutant Presenilin-1 Induces Apoptosis and Downregulates Akt/PKB
J. Neurosci., July 1, 1999; 19(13): 5360 - 5369.
[Abstract] [Full Text] [PDF]
P. Arduengo, O. Appleberry, P Chuang, and S. L'Hernault
The presenilin protein family member SPE-4 localizes to an ER/Golgi derived organelle and is required for proper cytoplasmic partitioning during Caenorhabditis elegans spermatogenesis
J. Cell Sci., June 14, 1999; 111(24): 3645 - 3654.
[Abstract] [PDF]
C. A. Saura, T. Tomita, F. Davenport, C. L. Harris, T. Iwatsubo, and G. Thinakaran
Evidence That Intramolecular Associations between Presenilin Domains Are Obligatory for Endoproteolytic Processing
J. Biol. Chem., May 14, 1999; 274(20): 13818 - 13823.
[Abstract] [Full Text] [PDF]
C.-S. Hong, L. Caromile, Y. Nomata, H. Mori, D. E. Bredesen, and E. H. Koo
Contrasting Role of Presenilin-1 and Presenilin-2 in Neuronal Differentiation In Vitro
J. Neurosci., January 15, 1999; 19(2): 637 - 643.
[Abstract] [Full Text] [PDF]
J. A. Johnston, C. L. Ward, and R. R. Kopito
Aggresomes: A Cellular Response to Misfolded Proteins
J. Cell Biol., December 28, 1998; 143(7): 1883 - 1898.
[Abstract] [Full Text] [PDF]
G. Wu, E. J. A. Hubbard, J. K. Kitajewski, and I. Greenwald
Evidence for functional and physical association between Caenorhabditis elegans SEL-10, a Cdc4p-related protein, and SEL-12 presenilin
PNAS, December 22, 1998; 95(26): 15787 - 15791.
[Abstract] [Full Text] [PDF]
Q. Guo, N. Robinson, and M. P. Mattson
Secreted beta -Amyloid Precursor Protein Counteracts the Proapoptotic Action of Mutant Presenilin-1 by Activation of NF-kappa B and Stabilization of Calcium Homeostasis
J. Biol. Chem., May 15, 1998; 273(20): 12341 - 12351.
[Abstract] [Full Text] [PDF]
G. Thinakaran, C. L. Harris, T. Ratovitski, F. Davenport, H. H. Slunt, D. L. Price, D. R. Borchelt, and S. S. Sisodia
Evidence That Levels of Presenilins (PS1 and PS2) Are Coordinately Regulated by Competition for Limiting Cellular Factors
J. Biol. Chem., November 7, 1997; 272(45): 28415 - 28422.
[Abstract] [Full Text] [PDF]
T. Ratovitski, H. H. Slunt, G. Thinakaran, D. L. Price, S. S. Sisodia, and D. R. Borchelt
Endoproteolytic Processing and Stabilization of Wild-type and Mutant Presenilin
J. Biol. Chem., September 26, 1997; 272(39): 24536 - 24541.
[Abstract] [Full Text] [PDF]
N. Mitsuda, A. D. Roses, and M. P. Vitek
Transcriptional Regulation of the Mouse Presenilin-1 Gene
J. Biol. Chem., September 19, 1997; 272(38): 23489 - 23497.
[Abstract] [Full Text] [PDF]
W. A. Maltese, S. Wilson, Y. Tan, S. Suomensaari, S. Sinha, R. Barbour, and L. McConlogue
Retention of the Alzheimer's Amyloid Precursor Fragment C99 in the Endoplasmic Reticulum Prevents Formation of Amyloid beta -Peptide
J. Biol. Chem., June 1, 2001; 276(23): 20267 - 20279.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|