gamma-secretase cleaves the p75NTR transmembrane domain Authored: Nasi, S, Annibali, D, 2006-10-10 09:07:07 Edited: Jassal, B, 2008-05-20 12:26:36 Pubmed12843241 Reactome Database ID Release 43193682 Reactome, http://www.reactome.org ReactomeREACT_13609 Reviewed: Chao, MV, 2008-05-28 09:46:01 Reviewed: Friedman, WJ, 2008-05-20 12:23:46 Within early endosomes, p75NTR C-Terminal Fragment undergoes processing by gamma-secretase, a complex composed of a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PEN2. Such a minimal complex is sufficient for secretase activity, although other components may exist. The p75NTR cleavage by gamma-secretase gives rise to a 20-kD ICD (IntraCellular Domain) fragment, and to a small peptide, the significance of which is unknown but that is analogous to the A-beta peptides generated from amyloid precursor protein. p75NTR ICD may have cytoplasmic and nuclear signalling functions and it is unstable.