Phospholipase D1 is associated with amyloid precursor protein in Alzheimer's disease.
Amyloid precursor protein (APP) is a widely expressed transmembrane protein of unknown function that is involved in the pathogenesis of Alzheimer's disease (AD). We investigated the involvement of phospholipase D (PLD) in the pathophysiology of AD. We showed dramatic upregulation of PLD1 immunoreactivity in reactive astroglial cells in brain tissue sections from authentic AD patients. Expression and activity of PLD1 were up-regulated in brain tissues from AD patients, especially caveolae membrane fraction, compared with those of control brains. Interestingly, PLD1 physically interacts and colocalizes with APP and caveolin-3. We found that APP was associated with the pleckstrin homology domain of PLD1, and the amyloid region of APP interacted with PLD. Elevated expression of APP stimulated PLD activity in human astroglioma cells. These results suggest that up-regulation of PLD might have a role in the neuronal pathology associated with AD.
Jin
Jae-Kwang
JK
Ilsong Institute of Life Science, Hallym University, Kwanyang-dong, Dongan-gu, Anyang, Kyonggi-do, Republic of Korea.
Ahn
Bong-Hyun
BH
Na
Yeo-Jung
YJ
Kim
Jae-Il
JI
Kim
Yong-Sun
YS
Choi
Eun-Kyoung
EK
Ko
Young-Gyu
YG
Chung
Kwang Chul
KC
Kozlowski
Piotr B
PB
Min
Do Sik
do S
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001254:Astrocytoma; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D051244:Caveolin 3 / Q000378:metabolism; D002460:Cell Line; D002522:Chlorocebus aethiops; D005260:Female; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D016296:Mutagenesis / Q000502:physiology; D010739:Phospholipase D / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D011180:Postmortem Changes; D014162:Transfection / Q000379:methods; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D016564:Amyloid beta-Protein Precursor; D001798:Blood Proteins; D051244:Caveolin 3; D010750:Phosphoproteins; C039077:platelet protein P47; D010739:Phospholipase D; C106801:phospholipase D1