Jg. Culvenor et al., ALZHEIMERS-DISEASE-ASSOCIATED PRESENILIN-1 IN NEURONAL CELLS - EVIDENCE FOR LOCALIZATION TO THE ENDOPLASMIC-RETICULUM GOLGI INTERMEDIATE COMPARTMENT, Journal of neuroscience research, 49(6), 1997, pp. 719-731
The recently identified Alzheimer's disease-associated presenilin 1 an
d 2 (PS1 and PS2) genes encode two homologous multi membrane-spanning
proteins, Rabbit antibodies to the N-terminal domain of PS1 detected P
S1 in human neuroblastoma SH-SY5Y wild type and PS1 transfectants (SY5
Y-PS1) as well as in mouse P19, in CHO-K1 and CHO-APP770 transfected c
ells, in rat cerebellar granule and hippocampal neurons, and astrocyte
s, Immunoblotting detected full-length protein of 50 kDa, and a major
presumptive cleavage product of 30 kDa, The immunofluorescence pattern
resembled labeling of the endoplasmic reticulum-Golgi intermediate co
mpartment (ERGIC) marker protein ERGIC-53, PS1 distribution showed sli
ght condensation after brefeldin A and more marked condensation after
incubation of cells at 16 degrees C, characteristic of the ERGIC compa
rtment, Double labeling showed colocalization of ERGIC-53 with PS1 in
the SY5Y-PS1 cells, PS1 labeling of SY5Y-PS1 and P19 cells showed over
lap of the cis-Golgi marker p210 and colocalization with p210 after br
efeldin A which causes redistribution of p210 to the ERGIC, Expression
of PS1 did not change in level or cellular distribution during develo
pment of neurons in culture, Double labeling for the amyloid precursor
protein (APP) and PS1 on SY5Y-PS1 cells and CHO-APP770 cells showed s
ome overlap under control conditions, These results indicate that PS1
is a resident protein of the ERGIC and could be involved in traffickin
g of proteins, including APP, between the ER and Golgi compartments. (
C) 1997 Wiley-Liss, Inc.