Abstract |
In a previous study, we reported that Alzheimer's disease-associated presenilin-2 interacts with a LIM-domain protein, namely, DRAL/FHL2/SLIM3. In this study, we investigated whether DRAL modifies the metabolism of the amyloid precursor protein (APP). We used small interfering RNA ( siRNA) to knockdown DRAL in COS7 and HEK293 cells that stably overexpress APP695. We found that the knockdown was accompanied by a decrease in the amount of secreted alpha-secretase-cleaved APP and the membrane-bound C-terminal fragment C83 and an increase in the amount of secreted beta-amyloid peptide (Abeta) from the cells. We also found that in addition to a disintegrin and metalloprotease (ADAM)-17, DRAL binds to ADAM-10. Thus, DRAL may be involved in the processing of APP through the alpha-secretase pathway.
|
Authors | Hiroshi Tanahashi, Katsuji Yoshioka |
Journal | Neuroscience letters
(Neurosci Lett)
Vol. 439
Issue 3
Pg. 293-7
(Jul 18 2008)
ISSN: 0304-3940 [Print] Ireland |
PMID | 18534756
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Amyloid beta-Protein Precursor
- FHL2 protein, human
- Homeodomain Proteins
- LIM-Homeodomain Proteins
- Membrane Proteins
- Muscle Proteins
- Phorbol Esters
- Prostanoic Acids
- RNA, Small Interfering
- Transcription Factors
- phorbol-12-myristate
- Amyloid Precursor Protein Secretases
- ADAM Proteins
- ADAM10 Protein
- ADAM10 protein, human
- ADAM17 Protein
- ADAM17 protein, human
- rosaprostol
|
Topics |
- ADAM Proteins
(metabolism)
- ADAM10 Protein
- ADAM17 Protein
- Amyloid Precursor Protein Secretases
(metabolism)
- Amyloid beta-Protein Precursor
(metabolism)
- Animals
- Cell Line, Transformed
- Chlorocebus aethiops
- Cricetinae
- Homeodomain Proteins
(metabolism)
- Humans
- LIM-Homeodomain Proteins
- Membrane Proteins
(metabolism)
- Muscle Proteins
(metabolism)
- Phorbol Esters
(pharmacology)
- Prostanoic Acids
(metabolism)
- RNA, Small Interfering
(metabolism)
- Transcription Factors
(metabolism)
- Transfection
|