Expression and analysis of presenilin 1 in a human neuronal system: localization in cell bodies and dendrites - PubMed (original) (raw)

Comparative Study

Expression and analysis of presenilin 1 in a human neuronal system: localization in cell bodies and dendrites

D G Cook et al. Proc Natl Acad Sci U S A. 1996.

Abstract

Mutations in the recently identified presenilin 1 gene on chromosome 14 cause early onset familial Alzheimer disease (FAD). Herein we describe the expression and analysis of the protein coded by presenilin 1 (PS1) in NT2N neurons, a human neuronal model system. PS1 was expressed using recombinant Semliki Forest virions and detected by introduced antigenic tags or antisera to PS1-derived peptides. Immunoprecipitation revealed two major PS1 bands of approximately 43 and 50 kDa, neither of which were N-glycosylated or O-glycosylated. Immunoreactive PS1 was detected in cell bodies and dendrites of NT2N neurons but not in axons or on the cell surface. PS1 was also detected in BHK cells, where it was also intracellular and colocalized with calnexin, a marker for the rough endoplasmic reticulum. A mutant form of PS1 linked to FAD did not differ from the wild-type protein at the light microscopic level. The model system described here will enable studies of the function of PS1 in human neurons and the role of mutant PS1 in FAD.

PubMed Disclaimer

Similar articles

• Developmental expression of wild-type and mutant presenilin-1 in hippocampal neurons from transgenic mice: evidence for novel species-specific properties of human presenilin-1.
  Lévesque L, Annaert W, Craessaerts K, Mathews PM, Seeger M, Nixon RA, Van Leuven F, Gandy S, Westaway D, St George-Hyslop P, De Strooper B, Fraser PE. Lévesque L, et al. Mol Med. 1999 Aug;5(8):542-54. Mol Med. 1999. PMID: 10501657 Free PMC article.
• Processing of wild-type and mutant familial Alzheimer's disease-associated presenilin-1 in cultured neurons.
  Weihl CC, Ghadge GD, Miller RJ, Roos RP. Weihl CC, et al. J Neurochem. 1999 Jul;73(1):31-40. doi: 10.1046/j.1471-4159.1999.0730031.x. J Neurochem. 1999. PMID: 10386952
• The presenilin-1 familial Alzheimer disease mutant P117L impairs neurogenesis in the hippocampus of adult mice.
  Wen PH, Hof PR, Chen X, Gluck K, Austin G, Younkin SG, Younkin LH, DeGasperi R, Gama Sosa MA, Robakis NK, Haroutunian V, Elder GA. Wen PH, et al. Exp Neurol. 2004 Aug;188(2):224-37. doi: 10.1016/j.expneurol.2004.04.002. Exp Neurol. 2004. PMID: 15246822
• Alzheimer's disease-associated presenilin 1 in neuronal cells: evidence for localization to the endoplasmic reticulum-Golgi intermediate compartment.
  Culvenor JG, Maher F, Evin G, Malchiodi-Albedi F, Cappai R, Underwood JR, Davis JB, Karran EH, Roberts GW, Beyreuther K, Masters CL. Culvenor JG, et al. J Neurosci Res. 1997 Sep 15;49(6):719-31. doi: 10.1002/(SICI)1097-4547(19970915)49:6<719::AID-JNR6>3.0.CO;2-A. J Neurosci Res. 1997. PMID: 9335259
• Expression of foreign proteins in a human neuronal system.
  Cook DG, Lee VM, Doms RW. Cook DG, et al. Methods Cell Biol. 1994;43 Pt A:289-303. doi: 10.1016/s0091-679x(08)60609-3. Methods Cell Biol. 1994. PMID: 7823867 Review.

Cited by

• Presenilin 1 controls gamma-secretase processing of amyloid precursor protein in pre-golgi compartments of hippocampal neurons.
  Annaert WG, Levesque L, Craessaerts K, Dierinck I, Snellings G, Westaway D, George-Hyslop PS, Cordell B, Fraser P, De Strooper B. Annaert WG, et al. J Cell Biol. 1999 Oct 18;147(2):277-94. doi: 10.1083/jcb.147.2.277. J Cell Biol. 1999. PMID: 10525535 Free PMC article.
• Use of yeast as a model system to investigate protein conformational diseases.
  Coughlan CM, Brodsky JL. Coughlan CM, et al. Mol Biotechnol. 2005 Jun;30(2):171-80. doi: 10.1385/MB:30:2:171. Mol Biotechnol. 2005. PMID: 15920289 Review.
• Alphaviral vectors for gene transfer into neurons.
  Ehrengruber MU. Ehrengruber MU. Mol Neurobiol. 2002 Oct-Dec;26(2-3):183-201. doi: 10.1385/MN:26:2-3:183. Mol Neurobiol. 2002. PMID: 12428755 Review.
• Presenilins and APP in neuritic and synaptic plasticity: implications for the pathogenesis of Alzheimer's disease.
  Chan SL, Furukawa K, Mattson MP. Chan SL, et al. Neuromolecular Med. 2002;2(2):167-96. doi: 10.1385/NMM:2:2:167. Neuromolecular Med. 2002. PMID: 12428810 Review.
• Closing in on the amyloid cascade: recent insights into the cell biology of Alzheimer's disease.
  Huse JT, Doms RW. Huse JT, et al. Mol Neurobiol. 2000 Aug-Dec;22(1-3):81-98. doi: 10.1385/MN:22:1-3:081. Mol Neurobiol. 2000. PMID: 11414282 Review.

References

1. 1. J Neurochem. 1989 Dec;53(6):1910-7 - PubMed
2. 1. Proc Natl Acad Sci U S A. 1987 May;84(9):2688-92 - PubMed
3. 1. Methods Enzymol. 1990;191:841-54 - PubMed
4. 1. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7552-6 - PubMed
5. 1. Biotechnology (N Y). 1991 Dec;9(12):1356-61 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Atypon
  • Europe PubMed Central
  • PubMed Central

• Other Literature Sources

  • The Lens - Patent Citations Database

• Medical

  • MedlinePlus Health Information