Expression of reticulon 3 in Alzheimer's disease brain.
OBJECTIVE
Reticulon 3 (RTN3), a member of the reticulon family of proteins, interacts with the beta-secretase, beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1), and inhibits its activity to produce beta-amyloid protein. The aim of the present study was to clarify the biological role of RTN3 in the brain and its potential involvement in the neuropathology of Alzheimer's disease (AD).


METHODS
We performed immunohistochemical and biochemical analyses using a specific antibody against RTN3 to investigate the expression and subcellular localization of RTN3 in control and AD brain tissue samples.


RESULTS
Western blot analysis revealed no significant differences in the RTN3 levels between control and AD brains. Immunohistochemical staining showed that RTN3 immunoreactivity was predominantly localized in pyramidal neurones of the cerebral cortex. The patterns of RTN3 immunostaining were similar in control and AD cerebral cortices, and senile plaques were generally negative for RTN3. Biochemical subcellular fractionation disclosed that RTN3 colocalized with BACE1 in various fractions, including the endoplasmic reticulum and the Golgi apparatus. Double-immunofluorescence staining additionally indicated that RTN3 was localized in both endoplasmic reticulum and Golgi compartments in neurones.


CONCLUSIONS
These results show that RTN3 is primarily expressed in pyramidal neurones of the human cerebral cortex and that no clear difference of RTN3 immunoreactivity is observable between control and AD brains. Our data also suggest that there is considerable colocalization of RTN3 with BACE1 at a subcellular level.
Kume
H
H
Department of Demyelinating Disease and Ageing, National Institute of Neuroscience, NCNP, Tokyo, Japan.
Konishi
Y
Y
Murayama
K S
KS
Kametani
F
F
Araki
W
W
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism
D002352:Carrier Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C476198:RTN3 protein, human; C482720:Rtn3 protein, mouse; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse