Localization and trafficking of endogenous anterior pharynx-defective 1, a component of Alzheimer's disease related gamma-secretase.
Anterior pharynx-defective 1 (Aph-1) is a multi-spanning membrane protein and an integral component of the high molecular weight gamma-secretase complex that also contains presenilin, nicastrin, and Pen-2. In order to clarify the existence of an endogenous fragment of Aph-1 and dissect the localization and processing of endogenous Aph-1 proteins, we examined cell lines and primary cell cultures with our own carboxyl terminal-specific antibodies for Aph-1aL. Fractionation and immunofluorescence studies indicated that the endogenous full-length Aph-1aL isoform localizes primarily to the endoplasmic reticulum as well as Golgi intermediate compartment, but small amount of it was detected at Golgi apparatus where most of its carboxyl terminal domain fragment existed. In primary neuronal and glial cultures, Aph-1aL was present in the neurites and glial cell processes. Endogenous Aph-1a and its proteolytic fragment have unique properties for cleavage control that may have implications for gamma-secretase regulation and intracellular distribution.
Sanjo
Nobuo
N
Centre for Research in Neurodegenerative Diseases, University of Toronto, 6 Queen's Park Crescent West, Toronto, Ontario M5S 3H2, Canada. n-sanjo.nuro@tmd.ac.jp
Katayama
Taiichi
T
Hasegawa
Hiroshi
H
Jin
Haifeng
H
Duthie
Monika
M
Mount
Howard T J
HT
Mizusawa
Hidehiro
H
St George-Hyslop
Peter
P
Fraser
Paul E
PE
D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D000818:Animals; D002458:Cell Fractionation; D002460:Cell Line; D002478:Cells, Cultured; D010450:Endopeptidases; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D021381:Protein Transport
D008565:Membrane Proteins; C475154:APH1A protein, human; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D010447:Peptide Hydrolases