PT  - JOURNAL ARTICLE
AU  - Huanmian Chen
AU  - Henry L. Puhl III
AU  - Shui-Lin Niu
AU  - Drake C. Mitchell
AU  - Stephen R. Ikeda
TI  - Expression of Rem2, an RGK Family Small GTPase, Reduces N-Type Calcium Current without Affecting Channel Surface Density
AID  - 10.1523/JNEUROSCI.3111-05.2005
DP  - 2005 Oct 19
TA  - The Journal of Neuroscience
PG  - 9762--9772
VI  - 25
IP  - 42
4099  - http://www.jneurosci.org/content/25/42/9762.short
4100  - http://www.jneurosci.org/content/25/42/9762.full
SO  - J. Neurosci.2005 Oct 19; 25
AB  - Rad, Gem/Kir, Rem, and Rem2 are members of the Ras-related RGK (Rad, Gem, and Kir) family of small GTP-binding proteins. Heterologous expression of RGK proteins interferes with de novo calcium channel assembly/trafficking and dramatically decreases the amplitude of currents arising from preexisting high-voltage-activated calcium channels. These effects probably result from the direct interaction of RGK proteins with calcium channel β subunits. Among the RGK family, Rem2 is the only member abundantly expressed in neuronal tissues. Here, we examined the ability of Rem2 to modulate endogenous voltage-activated calcium channels in rat sympathetic and dorsal root ganglion neurons. Heterologous expression of Rem2 nearly abolished calcium currents arising from preexisting high-voltage-activated calcium channels without affecting low-voltage-activated calcium channels. Rem2 inhibition of N-type calcium channels required both the Ras homology (core) domain and the polybasic C terminus. Mutation of a putative GTP/Mg2+ binding motif in Rem2 did not affect suppression of calcium currents. Loading neurons with GDP-β-S via the patch pipette did not reverse Rem2-mediated calcium channel inhibition. Finally, [125I]Tyr22-ω-conotoxin GVIA cell surface binding in tsA201 cells stably expressing N-type calcium channels was not altered by Rem2 expression at a time when calcium current was totally abolished. Together, our results support a model in which Rem2 localizes to the plasma membrane via a C-terminal polybasic motif and interacts with calcium channel β subunits in the preassembled N-type channel, thereby forming a nonconducting species.