ADAM19 is tightly associated with constitutive Alzheimer's disease APP alpha-secretase in A172 cells.
To elucidate whether new proteases are involved in the processing of amyloid precursor protein (APP), we examined catalytically active ADAM12 and ADAM19 as candidates alpha-secretases. The overexpression of ADAM19 in HEK293 cells resulted in an increase in sAPPalpha. Therefore, we suggest that ADAM19 has a constitutive alpha-secretase activity. We examined regulated alpha-secretase activity by adding phorbol 12-myristate 13-acetate (PMA), but no regulated activity was found. To verify that endogenous ADAM19 has an APP alpha-secretase activity, we examined whether the constitutive level of alpha-secretase activity was reduced by RNA interference with ADAM19 in A172 cells. The amount of secreted sAPPalpha decreased by about 21% following RNAi. These results suggest that ADAM19 has a constitutive alpha-secretase activity for APP.
Tanabe
Chiaki
C
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan.
Hotoda
Nika
N
Sasagawa
Noboru
N
Sehara-Fujisawa
Atsuko
A
Maruyama
Kei
K
Ishiura
Shoichi
S
D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000072199:ADAM12 Protein; D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D014162:Transfection
D018076:DNA, Complementary; D008565:Membrane Proteins; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human; C411902:ADAM19 protein, human