Is gamma-secretase a multienzyme complex for membrane protein degradation? Models and speculations.
The beta- and gamma-secretases cleave the amyloid protein precursor (APP) to release the amyloid protein (Abeta). While the beta-secretase has now been identified, the gamma-secretase remains an enigma. A number of mutations in the presenilins (PS) and APP have been shown to alter the cleavage specificity of gamma-secretase. However, the relationship between PS and gamma-secretase remains unclear. This article presents some models of gamma-secretase and suggests that the simplest interpretation of current data is that gamma-secretase is a complex of several proteases located in the lumen of secretory vesicles.
Laboratory of Molecular Neurobiology, Department of Pathology, University of Melbourne, Victoria 3010, Australia. davidhs@unimelb.edu.au
David H
DH
Small
D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000737:chemistry; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008956:Models, Chemical; D008962:Models, Theoretical; D009097:Multienzyme Complexes; D022142:Secretory Vesicles / Q000201:enzymology
D016229:Amyloid beta-Peptides; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human