TY - JOUR T1 - The Stargazin-Related Protein γ7 Interacts with the mRNA-Binding Protein Heterogeneous Nuclear Ribonucleoprotein A2 and Regulates the Stability of Specific mRNAs, Including Ca<sub>V</sub>2.2 JF - The Journal of Neuroscience JO - J. Neurosci. SP - 10604 LP - 10617 DO - 10.1523/JNEUROSCI.2709-08.2008 VL - 28 IS - 42 AU - Laurent Ferron AU - Anthony Davies AU - Karen M. Page AU - David J. Cox AU - Jerôme Leroy AU - Dominic Waithe AU - Adrian J. Butcher AU - Priya Sellaturay AU - Steven Bolsover AU - Wendy S. Pratt AU - Fraser J. Moss AU - Annette C. Dolphin Y1 - 2008/10/15 UR - http://www.jneurosci.org/content/28/42/10604.abstract N2 - The role(s) of the novel stargazin-like γ-subunit proteins remain controversial. We have shown previously that the neuron-specific γ7 suppresses the expression of certain calcium channels, particularly CaV2.2, and is therefore unlikely to operate as a calcium channel subunit. We now show that the effect of γ7 on CaV2.2 expression is via an increase in the degradation rate of CaV2.2 mRNA and hence a reduction of CaV2.2 protein level. Furthermore, exogenous expression of γ7 in PC12 cells also decreased the endogenous CaV2.2 mRNA level. Conversely, knockdown of endogenous γ7 with short-hairpin RNAs produced a reciprocal enhancement of CaV2.2 mRNA stability and an increase in endogenous calcium currents in PC12 cells. Moreover, both endogenous and expressed γ7 are present on intracellular membranes, rather than the plasma membrane. The cytoplasmic C terminus of γ7 is essential for all its effects, and we show that γ7 binds directly via its C terminus to a heterogeneous nuclear ribonucleoprotein (hnRNP A2), which also binds to a motif in CaV2.2 mRNA, and is associated with native CaV2.2 mRNA in PC12 cells. The expression of hnRNP A2 enhances CaV2.2 I Ba, and this enhancement is prevented by a concentration of γ7 that alone has no effect on I Ba. The effect of γ7 is selective for certain mRNAs because it had no effect on α2δ-2 mRNA stability, but it decreased the mRNA stability for the potassium-chloride cotransporter, KCC1, which contains a similar hnRNP A2 binding motif to that in CaV2.2 mRNA. Our results indicate that γ7 plays a role in stabilizing CaV2.2 mRNA. ER -