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(Received for publication, May 30, 1996, and in revised form, October 1, 1996)
From the Presenilins 1 and 2 are unglycosylated proteins
with apparent molecular mass of 45 and 50 kDa, respectively, in
transfected COS-1 and Chinese hamster ovary cells. They colocalize with
proteins from the endoplasmic reticulum and the Golgi apparatus in
transfected and untransfected cells. In COS-1 cells low amounts of
intact endogeneous presenilin 1 migrating at 45 kDa are detected
together with relative larger amounts of presenilin 1 fragments
migrating between 18 and 30 kDa. The presenilins have a strong tendency to form aggregates (mass of 100-250 kDa) in SDS-polyacrylamide gel
electrophoresis, which can be partially resolved when denatured by SDS
at 37 °C instead of 95 °C. Sulfation, glycosaminoglycan modification, or acylation of the presenilins was not observed, but
both proteins are posttranslationally phosphorylated on serine residues. The mutations Ala-246
Volume 272, Number 6,
Issue of February 7, 1997
pp. 3590-3598
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
,
,
,
,
,
Experimental Genetics Group and
Molecular Oncology Group, Scios Inc.,
Sunnyvale, California 94043
Glu or Cys-410 Tyr that cause Alzheimer's disease do not interfere with the biosynthesis or phosphorylation of presenilin 1. Finally, using low concentrations of
digitonin to selectively permeabilize the cell membrane but not the
endoplasmic reticulum membrane, it is demonstrated that the two major
hydrophilic domains of presenilin 1 are oriented to the cytoplasm. The
current investigation documents the posttranslational modifications and
subcellular localization of the presenilins and indicates that
postulated interactions with amyloid precursor protein metabolism
should occur in the early compartments of the biosynthetic pathway.
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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]
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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]
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 M. P. Mattson and Qing Guo {blacksquare} REVIEW : The Presenilins Neuroscientist, March 1, 1999; 5(2): 112 - 124. [Abstract] [PDF]
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J. Walter, A. Schindzielorz, J. Grunberg, and C. Haass Phosphorylation of presenilin-2 regulates its cleavage by caspases and retards progression of apoptosis PNAS, February 16, 1999; 96(4): 1391 - 1396. [Abstract] [Full Text] [PDF]
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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]
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E. Jaikaran, G Marcon, L Levesque, P. George-Hyslop, P. Fraser, and A Clark Localisation of presenilin 2 in human and rodent pancreatic islet beta-cells; Met239Val presenilin 2 variant is not associated with diabetes in man J. Cell Sci., January 7, 1999; 112(13): 2137 - 2144. [Abstract] [PDF]
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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]
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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]
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H. Steiner, A. Capell, B. Pesold, M. Citron, P. M. Kloetzel, D. J. Selkoe, H. Romig, K. Mendla, and C. Haass Expression of Alzheimer's Disease-associated Presenilin-1 Is Controlled by Proteolytic Degradation and Complex Formation J. Biol. Chem., November 27, 1998; 273(48): 32322 - 32331. [Abstract] [Full Text] [PDF]
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A. Smine, X. Xu, K. Nishiyama, T. Katada, P. Gambetti, S. P. Yadav, X. Wu, Y.-C. Shi, S. Yasuhara, V. Homburger, et al. Regulation of Brain G-protein Go by Alzheimer's Disease Gene Presenilin-1 J. Biol. Chem., June 26, 1998; 273(26): 16281 - 16288. [Abstract] [Full Text] [PDF]
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G. Yu, F. Chen, G. Levesque, M. Nishimura, D.-M. Zhang, L. Levesque, E. Rogaeva, D. Xu, Y. Liang, M. Duthie, et al. The Presenilin 1 Protein Is a Component of a High Molecular Weight Intracellular Complex That Contains beta -Catenin J. Biol. Chem., June 26, 1998; 273(26): 16470 - 16475. [Abstract] [Full Text] [PDF]
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J. N. Keller, Q. Guo, F. W. Holtsberg, A. J. Bruce-Keller, and M. P. Mattson Increased Sensitivity to Mitochondrial Toxin-Induced Apoptosis in Neural Cells Expressing Mutant Presenilin-1 Is Linked to Perturbed Calcium Homeostasis and Enhanced Oxyradical Production J. Neurosci., June 15, 1998; 18(12): 4439 - 4450. [Abstract] [Full Text] [PDF]
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X. Li and I. Greenwald Additional evidence for an eight-transmembrane-domain topology for Caenorhabditis elegans and human presenilins PNAS, June 9, 1998; 95(12): 7109 - 7114. [Abstract] [Full Text] [PDF]
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J. Zhang, D. E. Kang, W. Xia, M. Okochi, H. Mori, D. J. Selkoe, and E. H. Koo Subcellular Distribution and Turnover of Presenilins in Transfected Cells J. Biol. Chem., May 15, 1998; 273(20): 12436 - 12442. [Abstract] [Full Text] [PDF]
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N. N. Dewji and S. J. Singer The seven-transmembrane spanning topography of the Alzheimer disease-related presenilin proteins in the plasma membranes of cultured cells PNAS, December 9, 1997; 94(25): 14025 - 14030. [Abstract] [Full Text] [PDF]
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