Selective up-regulation of alpha 1-chimaerin mRNA in SK-N-SH neuroblastoma cells by K+/-induced depolarisation.
The expression of alpha 1-chimaerin, which encodes a neuron-specific GTPase-activating protein for p21rac, is spatially and temporally regulated in vivo. In vitro, expression of the mRNA of both alpha 1-chimaerin and its alternative spliced form, alpha 2-chimaerin, was up-regulated when human neuroblastoma SK-N-SH cells underwent neuronal-type differentiation in a serum-free medium. KCl-induced membrane depolarisation also specifically up-regulated alpha 1-chimaerin mRNA expression in SK-N-SH cells at the transcriptional level. The up-regulation of alpha 1-chimaerin expression by membrane depolarisation is not an immediate early event, and occurs 3 h after KCl treatment. It does not require de novo protein synthesis. The increase in calcium influx via the L-type voltage-sensitive calcium channel as the result of depolarisation is a key event leading to the up-regulation of alpha 1-chimaerin mRNA. alpha 1-Chimaerin expression was also found to respond positively to the hypertonic osmolarity changes. These results suggest that in vivo expression of alpha 1-chimaerin, a potential signal transduction molecule, may be regulated by neuronal/synaptic activity.
Dong
J M
JM
Glaxo-IMCB Group, Institute of Molecular and Cell Biology, National University of Singapore, Singapore.
Lim
L
L
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D020746:Calcium Channels, L-Type; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D016895:Culture Media, Serum-Free; D004247:DNA / Q000096:biosynthesis; D020690:GTPase-Activating Proteins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D009994:Osmolar Concentration; D011188:Potassium / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D016895:Culture Media, Serum-Free; D020690:GTPase-Activating Proteins; D012333:RNA, Messenger; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D004247:DNA; D009543:Nifedipine; D011188:Potassium; D013936:Thymidine