γ Secretase Antibody Sampler Kit #5887

Protocols

• 5643: Western Blotting, Immunoprecipitation (Magnetic)
• 5665: Western Blotting
• 7074: Western Blotting
• 8598: Western Blotting, Immunoprecipitation (Magnetic)
• 9979: Western Blotting, Immunoprecipitation (Magnetic)

The γ Secretase Antibody Sampler Kit provides an economical means of evaluating components of the gamma secretase complex. The kit contains enough primary and secondary antibodies to perform two western miniblot experiments.

Nicastrin (D38F9) Rabbit mAb, PEN2 (D6G8) Rabbit mAb, Presenilin 1 (D39D1) Rabbit mAb, and Presenilin 2 (D30G3) Rabbit mAb recognize endogenous levels of respective target proteins. Presenilin 1 (D39D1) Rabbit mAb may also detect a nonspecific band at 60 kDa.

Monoclonal antibodies are produced by immunizing animals with a recombinant protein specific to the carboxy terminus of human Presenilin 1 protein, a synthetic peptide corresponding to residues surrounding Val390 of human Nicastrin protein, a synthetic peptide corresponding to residues surrounding Leu92 of human PEN2 protein, or a synthetic peptide corresponding to residues surrounding Met323 of human Presenilin 2 protein.

The γ secretase protease complex interacts with and cleaves intramembrane substrates as an essential function for regulation of intracellular signaling and cell-cell interactions. This multiprotein complex is comprised of four integral membrane proteins, Presenilin, Nicastrin, Aph-1, and PEN2, all of which are essential for complete proteolytic activity (1). Presenilin 1 and presenilin 2 are transmembrane proteins belonging to the presenilin family. Mutation of presenilin genes has been linked to early onset of Alzheimer disease, probably due to presenilin’s associated γ-secretase activity for amyloid-β protein processing (2,3). Endogenous presenilin mainly exists in a heterodimeric complex formed from the endoproteolytically processed amino-terminal (34 kDa) and carboxy-terminal (~20, 22, 23 kDa) fragments (CTF) (3,4). Nicastrin is a transmembrane glycoprotein serving as an essential component of the γ-secretase complex (5,6). Nicastrin protein is physically associated with presenilin and plays an important role in stabilization and correct localization of presenilin to the membrane-bound γ-secretase complex (7). Nicastrin also serves as a docking site for γ-secretase substrates such as APP and Notch, directly binding to them and presenting them properly to γ-secretase to ensure the correct cleavage process (6,8). Presenilin Enhancer 2 (PEN2) is a small integral membrane glycoprotein that contains two recognized transmembrane domains. Both the N- and C-terminal domains are oriented into the lumen of the endoplasmic reticulum (9). PEN2 is an important part of the γ-secretase complex as its knock down results in reduced amounts of the complex, resulting in a loss of γ-secretase activity (10).

1. Yu, G. et al. (2000) Nature 407, 48-54.
2. Sala Frigerio, C. et al. (2005) J Neurol 252, 1033-6.
3. Hansson, C.A. et al. (2004) J Biol Chem 279, 51654-60.
4. Haass, C. and De Strooper, B. (1999) Science 286, 916-9.
5. Kimberly, W.T. et al. (2000) J. Biol. Chem. 275, 3173-3178.
6. Esler, W. P. et al. (2002) Proc. Natl. Acad. Sci. USA 99, 2720-2725.
7. Kim, T.W. et al. (1997) J. Biol. Chem. 272, 11006-11010.
8. Kopan, R. and Goate, A. (2002) Neuron 33, 321-324.
9. Chen, F. et al. (2001) Nat. Cell Biol. 3, 751-754.
10. Steiner, H. et al. (2002) J Biol Chem 277, 39062-5.

Data sheet (109KB)

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