Calmodulin bifurcates the local Ca2+ signal that modulates P/Q-type Ca2+ channels
| Autor: | David T. Yue, Rebecca S. Alvania, Tuck Wah Soong, Badr A. Alseikhan, Carla D. DeMaria |
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| Rok vydání: | 2001 |
| Předmět: |
Multidisciplinary
biology Voltage-dependent calcium channel Calmodulin Molecular Sequence Data Mutant chemistry.chemical_element Calcium Channels P-Type Calcium Recombinant Proteins Cav2.1 Cell Line Calcium Channels Q-Type chemistry Synaptic plasticity biology.protein Biophysics Humans Amino Acid Sequence Calcium Signaling Signal transduction Intracellular |
| Zdroj: | Nature. 411:484-489 |
| ISSN: | 1476-4687 0028-0836 |
| DOI: | 10.1038/35078091 |
| Popis: | Acute modulation of P/Q-type (α1A) calcium channels by neuronal activity-dependent changes in intracellular Ca2+ concentration may contribute to short-term synaptic plasticity1,2,3, potentially enriching the neurocomputational capabilities of the brain4,5. An unconventional mechanism for such channel modulation has been proposed6,7 in which calmodulin (CaM) may exert two opposing effects on individual channels, initially promoting (‘facilitation’) and then inhibiting (‘inactivation’) channel opening. Here we report that such dual regulation arises from surprising Ca2+-transduction capabilities of CaM. First, although facilitation and inactivation are two competing processes, both require Ca2+-CaM binding to a single ‘IQ-like’ domain on the carboxy tail of α1A8; a previously identified ‘CBD’ CaM-binding site6,7 has no detectable role. Second, expression of a CaM mutant with impairment of all four of its Ca2+-binding sites (CaM1234) eliminates both forms of modulation. This result confirms that CaM is the Ca2+ sensor for channel regulation, and indicates that CaM may associate with the channel even before local Ca2+ concentration rises. Finally, the bifunctional capability of CaM arises from bifurcation of Ca2+ signalling by the lobes of CaM: Ca2+ binding to the amino-terminal lobe selectively initiates channel inactivation, whereas Ca2+ sensing by the carboxy-terminal lobe induces facilitation. Such lobe-specific detection provides a compact means to decode local Ca2+ signals in two ways, and to separately initiate distinct actions on a single molecular complex. |
| Databáze: | OpenAIRE |
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