Activity-dependent increase in beta-amyloid precursor protein mRNA expression in neurons.
Although beta-amyloid precursor protein (APP) has been suggested to play a role in neuronal survival and plasticity, the mRNA expression of APP has not been studied in terms of neuronal activity. In cultures of mouse cerebellar granule cells, we found that the levels of APP mRNA increased when a high concentration of potassium was present in the medium. A deprivation of membrane depolarization caused by lowering the K+ concentration decreased both mRNA expression and protein synthesis of APP. Increasing the concentration, however, restored mRNA expression, which was driven by the influx of Ca2+ through L-type voltage-dependent calcium channels and mediated by de novo protein synthesis. Thus, APP mRNA expression is controlled in an activity-dependent manner in neurons.
Tabuchi
Akiko
A
Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Sugitani 2630, Toyama 930-0194, Japan.
Ishii
Asami
A
Fukuchi
Mamoru
M
Kobayashi
Sachiyo
S
Suzuki
Toshiharu
T
Tsuda
Masaaki
M
D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride / Q000378:metabolism / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*
D016564:Amyloid beta-Protein Precursor; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011189:Potassium Chloride; D002118:Calcium