γ Secretase Antibody Sampler Kit

Background

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).