Selective up-regulation of α1-chimaerin mRNA in SK-N-SH neuroblastoma cells by K+-induced depolarisation

Abstract

The expression of α1-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 α1-chimaerin and its alternative spliced form, α2-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 α1-chimaerin mRNA expression in SK-N-SH cells at the transcriptional level. The up-regulation of α1-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 α1-chimaerin mRNA. α1-Chimaerin expression was also found to respond positively to the hypertonic osmolarity changes. These results suggest that in vivo expression of α1-chimaerin, a potential signal transduction molecule, may be regulated by neuronal/synaptic activity.