Calcium channel beta subunits differentially regulate the inhibition of N-type channels by individual Gbeta isoforms
| Autor: | Zhong-Ping Feng, Clinton J. Doering, Michelle I. Arnot, Gerald W. Zamponi |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Patch-Clamp Techniques
Time Factors Protein subunit Recombinant Fusion Proteins Blotting Western Green Fluorescent Proteins Palmitic Acid chemistry.chemical_element Calcium N-type calcium channel Transfection Biochemistry Cell Line Heterotrimeric G protein Animals Humans Protein Isoforms Molecular Biology Neurons Microscopy Confocal Voltage-dependent calcium channel Calcium channel Brain Cell Biology Cell biology Protein Structure Tertiary Rats R-type calcium channel G beta-gamma complex Kinetics Luminescent Proteins chemistry Mutagenesis Site-Directed Calcium Channels Protein Binding |
| Zdroj: | The Journal of biological chemistry. 276(48) |
| ISSN: | 0021-9258 |
| Popis: | The direct inhibition of N- and P/Q-type calcium channels by G protein betagamma subunits is considered a key mechanism for regulating presynaptic calcium levels. We have recently reported that a number of features associated with this G protein inhibition are dependent on the G protein beta subunit isoform (Arnot, M. I., Stotz, S. C., Jarvis, S. E., Zamponi, G. W. (2000) J. Physiol. (Lond.) 527, 203-212; Cooper, C. B., Arnot, M. I., Feng, Z.-P., Jarvis, S. E., Hamid, J., Zamponi, G. W. (2000) J. Biol. Chem. 275, 40777-40781). Here, we have examined the abilities of different types of ancillary calcium channel beta subunits to modulate the inhibition of alpha(1B) N-type calcium channels by the five known different Gbeta subunit subtypes. Our data reveal that the degree of inhibition by a particular Gbeta subunit is strongly dependent on the specific calcium channel beta subunit, with N-type channels containing the beta(4) subunit being less susceptible to Gbetagamma-induced inhibition. The calcium channel beta(2a) subunit uniquely slows the kinetics of recovery from G protein inhibition, in addition to mediating a dramatic enhancement of the G protein-induced kinetic slowing. For Gbeta(3)-mediated inhibition, the latter effect is reduced following site-directed mutagenesis of two palmitoylation sites in the beta(2a) N-terminal region, suggesting that the unique membrane tethering of this subunit serves to modulate G protein inhibition of N-type calcium channels. Taken together, our data suggest that the nature of the calcium channel beta subunit present is an important determinant of G protein inhibition of N-type channels, thereby providing a possible mechanism by which the cellular/subcellular expression pattern of the four calcium channel beta subunits may regulate the G protein sensitivity of N-type channels expressed at different loci throughout the brain and possibly within a neuron. |
| Databáze: | OpenAIRE |
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