The role of the novel putative stargazin-like γ-subunits in relation to voltage-gated calcium channel function is controversial. We have previously cloned a member of this family, γ7, and found that it markedly reduced functional expression of CaV2.2 channels. Here we have shown the degradation rate of CaV2.2 mRNA is increased in the presence of human γ7 (after 9 hours with Actinomycin D: 45.8 ± 14 %, n=11, vs 11.9 ± 3.6 %, n=7, with γ7 and under control conditions, respectively; mean±SEM, P<0.05, Student's t-test). This process regulates the physiological level of CaV2.2 transcripts, since knockdown of endogenous γ7 with short hairpin RNA constructs in the neuron-like PC12 cell line markedly increased their endogenous CaV2.2 mRNA level. Interestingly, the knockdown of endogenous γ7 also affects neurite outgrowth of differentiated PC12 cells and native DRG neurons. We have shown that the reduction of neurite outgrowth is associated with modification of F-actin and GAP-43 distribution in growth cones. Our results support the hypothesis that γ7 is involved in the stability of specific mRNAs such as CaV2.2 and that this function is involved in neurite outgrowth.
Life Sciences 2007 (2007) Proc Life Sciences, PC171
Poster Communications: Regulation of N-type calcium channel transcript stability by the stargazin-related protein γ7
L. Ferron1, D. J. Cox1, J. Leroy1, K. M. Page1, M. Nieto-Rostro1, S. Bolsover2, A. J. Butcher1, A. Davies1, J. Gruendemann1, P. Sellaturay1, W. S
1. Pharmacology, UCL , London, United Kingdom. 2. Physiology, UCL, London, United Kingdom.
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