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.
Amieux, PS, Schecterson, LC, Wiley, JC, Hudson, M, Kanning, KC, Bothwell, M
endopeptidase activity of gamma-secretase complex [plasma membrane]
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