Figure 10 Alternative splicing generates transcripts for a voltage-gated calcium channel that code for truncated proteins. RT-PCR analyses indicate that the tunicate calcium channel gene expresses splice variants. One variant, TuCal, codes for a full-length calcium channel a-subunit. In contrast, the other variant, ATuCal, codes for a truncated subunitthat lacks a substantial portion of the N-terminal region. Okagaki et al. (2001) demonstrate that the truncated subunit acts in a dominant-negative manner and inhibits function of the full-length protein. Lane 1 is a positive control with whole-tadpole RNA. RT-PCR analyses for a sodium channel gene TuNal are shown for comparison. Lanes 2, 6, and 10 present analyses done using neuronal RNA. Lanes 3, 7, and 11 present analyses done using RNA from epidermal (non-neuronal) cells. Lanes 4, 8, and 12 present analyses done using RNA from cells giving rise to motor neurons. Lanes 5, 9, and 11 present analyses done using muscle cell RNA. Reproduced from Okagaki, R., Izumi, H., Okada, T., Nagahora, H., Nakajo, K., and Okamura, Y. 2001. The maternal transcript for truncated voltage-dependent Ca2+ channels in the ascidian embryo: A potential suppressive role in Ca2+ channel expression. Dev. Biol. 230, 258-277, with permission from Elsevier.
220.127.116.11.2 Editing RNA editing leads to specific alterations in single nucleotides of mRNA transcripts (for review, see Simpson and Emerson, 1996). Selective mRNA editing of VGIC transcripts during development has been observed for sodium channels in invertebrates (Hanrahan et al., 2000; Song et al., 2004). The Drosophila para gene, in addition to being alternatively spliced, shows developmentally regulated patterns of RNA editing (Hanrahan et al., 2000). In the German cockroach, editing of the sodium gene BgNav transcripts occurs in a develop-mentally specific manner (Song et al., 2004). Furthermore, editing resulted in transcripts that coded for proteins that varied significantly in voltage-dependent activation and inactivation properties.
Ion channels display many different types of post-translational modifications that are linked to specific functional consequences. Here, we summarize examples of developmentally regulated post-translational modifications. For many cases, however, the potential physiological roles of post-translational modifications during development are poorly understood (but see Misonou et al., 2004). Post-translation mechanisms might be involved in setting current density levels in mature neurons (Blaine et al., 2004; Figure 11).
18.104.22.168.1 Surface membrane insertion One of the best-studied examples of post-translational control of excitability concerns regulation of large-conductance calcium-activated potassium (KCa) channels of chick ciliary ganglion neurons (for review, see Dryer, 1998; Dryer etal., 2003). Normal developmental upregula-tion of KCa channels requires interactions with both targets (iris) and inputs (afferent innervation provided by the Edinger-Westphal nucleus).
Transforming growth factor-01 (TGF-01) and neuregulin-1 mediate the effects of cell-cell interactions with targets and inputs, respectively, on KCa channels both in vitro and in vivo (Subramony et al., 1996; Cameron et al., 1998, 2001).
4 nA 20 ms
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