gamma Secretase Antibody Sampler Kit

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