Gene transcription and splicing of T-type channels are evolutionarily-conserved strategies for regulating channel expression and gating
| Autor: | J. David Spafford, Adriano Senatore |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Transcription
Genetic RNA Splicing Molecular Sequence Data Gene Expression Neurophysiology lcsh:Medicine Gating Biology Biochemistry Ion Channels Calcium Channels T-Type 03 medical and health sciences Exon 0302 clinical medicine Molecular Cell Biology Animals Humans Amino Acid Sequence lcsh:Science Gene 030304 developmental biology Genetics Regulation of gene expression 0303 health sciences Multidisciplinary Sequence Homology Amino Acid Voltage-dependent calcium channel HEK 293 cells lcsh:R Intron Proteins Neurochemistry Exons Cell biology Transmembrane Proteins Gene Expression Regulation Cellular Neuroscience RNA splicing lcsh:Q Molecular Neuroscience Ion Channel Gating 030217 neurology & neurosurgery Research Article Neuroscience |
| Zdroj: | PLoS ONE, Vol 7, Iss 6, p e37409 (2012) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | T-type calcium channels operate within tightly regulated biophysical constraints for supporting rhythmic firing in the brain, heart and secretory organs of invertebrates and vertebrates. The snail T-type gene, LCa(v)3 from Lymnaea stagnalis, possesses alternative, tandem donor splice sites enabling a choice of a large exon 8b (201 aa) or a short exon 25c (9 aa) in cytoplasmic linkers, similar to mammalian homologs. Inclusion of optional 25c exons in the III-IV linker of T-type channels speeds up kinetics and causes hyperpolarizing shifts in both activation and steady-state inactivation of macroscopic currents. The abundant variant lacking exon 25c is the workhorse of embryonic Ca(v)3 channels, whose high density and right-shifted activation and availability curves are expected to increase pace-making and allow the channels to contribute more significantly to cellular excitation in prenatal tissue. Presence of brain-enriched, optional exon 8b conserved with mammalian Ca(v)3.1 and encompassing the proximal half of the I-II linker, imparts a ~50% reduction in total and surface-expressed LCa(v)3 channel protein, which accounts for reduced whole-cell calcium currents of +8b variants in HEK cells. Evolutionarily conserved optional exons in cytoplasmic linkers of Ca(v)3 channels regulate expression (exon 8b) and a battery of biophysical properties (exon 25c) for tuning specialized firing patterns in different tissues and throughout development. |
| Databáze: | OpenAIRE |
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