RNA interference silencing of DRAL affects processing of amyloid precursor protein

• Published in: Neuroscience letters Vol. 439; no. 3; pp. 293 - 297
• Main Authors: Tanahashi, Hiroshi, Yoshioka, Katsuji
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 18.07.2008; Elsevier
• Subjects: ADAM Proteins - metabolism; ADAM-10/Kuzbanian; ADAM-17/TACE; ADAM10 Protein; ADAM17 Protein; Alzheimer's disease; Amyloid beta-Protein Precursor - metabolism; Amyloid precursor protein (APP); Amyloid Precursor Protein Secretases - metabolism; Animals; Biological and medical sciences; Cell Line, Transformed; Cercopithecus aethiops; Cricetinae; DRAL/FHL2/SLIM3; Fundamental and applied biological sciences. Psychology; 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; Vertebrates: nervous system and sense organs; α-Secretase; ADAM-10/Kuzbanian; α-Secretase; ADAM-17/TACE; DRAL/FHL2/SLIM3; Alzheimer's disease; Amyloid precursor protein (APP); α-Secretase;Alzheimer's disease;Amyloid precursor protein (APP);ADAM-10/Kuzbanian;ADAM-17/TACE;DRAL/FHL2/SLIM3; Amyloid precursor protein
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2008.05.039

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 α-secretase-cleaved APP and the membrane-bound C-terminal fragment C83 and an increase in the amount of secreted β-amyloid peptide (Aβ) 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 α-secretase pathway.