Direct binding of G-protein βλ complex to voltage-dependent calcium channels

  title={Direct binding of G-protein $\beta$$\lambda$ complex to voltage-dependent calcium channels},
  author={Michel de Waard and Hongyan Liu and Denise S Walker and Victoria E. Scott and Christina A. Gurnett and Kevin P. Campbell},
Voltage-dependent Ca2+ channels play a central role in controlling neurotransmitter release at the synapse1,2. They can be inhibited by certain G-protein-coupled receptors, acting by a pathway intrinsic to the membrane3–6. Here we show that this inhibition results from a direct interaction between the G-protein βλ complex and the pore-forming α1 subunits of several types of these channels7. The interaction is mediated by the cytoplasmic linker connecting the first and second transmembrane… 

Functional Role of a C-Terminal Gβγ-Binding Domain of Cav2.2 Channels

This work examines the functional relevance of a C-terminal binding site for Gbetagamma subunits on Ca(v)2.2b channels, which mediate N-type Ca(2+) currents, to influence the physiological responsiveness of Ca( 2+) channels to low-level G protein activation.

Competitive and Synergistic Interactions of G Protein β2 and Ca2+ Channel β1b Subunits with Cav2.1 Channels, Revealed by Mammalian Two-hybrid and Fluorescence Resonance Energy Transfer Measurements*

The results suggest that the G protein alters the orientation and/or association between the Ca2+ channel β and α12.1 subunits, which involves the C terminus of the α1 subunit and may corresponds to a new conformational state of the channel.

Structure of a complex between a voltage-gated calcium channel β-subunit and an α-subunit domain

Together, these data suggest that CaVβs influence CaV gating by direct modulation of IS6 movement within the channel pore, that has a critical role in CaV inactivation.

Determinants of G protein inhibition of presynaptic calcium channels

  • G. Zamponi
  • Biology, Chemistry
    Cell Biochemistry and Biophysics
  • 2007
The regulation of the activities of Presynaptic Ca channels is becoming increasingly complex, a feature that may contribute to the overall fine-tuning of Ca entry into presynaptic nerve termini, and thus, neurotransmission.

A New β Subtype-specific Interaction in α1ASubunit Controls P/Q-type Ca2+ Channel Activation*

This work describes a new subtype-specific interaction (Ss1) between the amino-terminal cytoplasmic domain of α1A (BI-2) and the carboxyl terminus of β4 and suggests a role in the specificity ofα1-β pairing.

Mechanisms of modulation of voltage‐dependent calcium channels by G proteins

Evidence suggests that this mechanism may be responsible for at least some of the presynaptic inhibition of synaptic transmission mediated by a wide variety of 7TM receptors in many areas of the nervous system.

T-type calcium channel regulation by specific G-protein βγ subunits

The α1H channel is identified as a new effector for G-protein βγ subunits, and the selective signalling roles available for particular βγ combinations are highlighted.

Determinants of the voltage dependence of G protein modulation within calcium channel β subunits

The main finding is that the CaVβ subunit GK domains, from either β1b or β2, are sufficient to restore voltage dependence to G protein modulation, and it is found that the removal of the variable HOOK region from β2a promotes tonic voltage-dependent Gprotein modulation.

G Protein Modulation of Voltage-Gated Calcium Channels

Evidence suggests a key role for the β subunits of calcium channels in the process of Gprotein modulation, and the role of a class of proteins termed “regulators of G protein signaling” will also be described.



Crosstalk between G proteins and protein kinase C mediated by the calcium channel α1 subunit

Crosstalk results from the PKC-dependent phosphorylation of one of the Gβλ binding sites which antagonizes G βλ-induced inhibition, providing a mechanism for the highly regulated and dynamic control of neurotransmitter release that depends on the integration of multiple presynaptic signals.

Properties of the - Anchoring Site in Voltage-dependent Ca Channels (*)

The results demonstrate that the site of interaction between AID and β subunit is responsible for anchoring the β sub unit to the α subunit and thus allowing theβ subunit to modify Ca channel activity.

Calcium channel β-subunit binds to a conserved motif in the I–II cytoplasmic linker of the α1-subunit

It is reported that the β-subunit binds to the cytoplasmic linker between repeats I and II of the dihydropyridine-sensitive α 1-sub units from skeletal and cardiac muscles, and also with the more distantly related neuronal α 1A and ω-conotoxin GVIA-sensitive aα 1B-subunits.

Voltage-dependent modulation of N-type calcium channels by G-protein β γsubunits

It is shown that transient overexpression of Gβγ in sympathetic neurons mimics and occludes the voltage-dependent Ca2+ channel modulation produced by noradrenaline (NA), and indicates that it is G βγ, and not Gα, that mediates voltage- dependent inhibition of N-type Ca 2+ channels.

Modulation of Ca2+ channels βγ G-protein py subunits

It is reported that Gβγ subunits can modulate Ca2+ channels and that overexpression of exogenous Gβ subunits is sufficient to cause channel modulation.

A region of adenylyl cyclase 2 critical for regulation by G protein beta gamma subunits.

The region defined by residues 956 to 982 of adenylyl cyclase 2 may contain determinants important for receiving signals from G beta gamma, which is conserved in regions of potassium channels and beta-adrenergic receptor kinases that participate in G beta Gamma interactions.

Recombinant G-protein βγ-subunits activate the muscarinic-gated atrial potassium channel

It is concluded that Gβγ is a primary regulator of IK.ACh activity and plays a major role in this pathway through muscarinic receptor binding and activation of pertussis-toxin-sensitive G proteins.

G-protein modulation of neuronal class E (alpha 1E) calcium channel expressed in GH3 cells.

Different types of neuronal Ca2+ channels can be modulated not only by a similar mechanism but also by a different mechanism conferring a multilateral regulation of Ca2- entry through these channels.

Inhibition of the interaction of G protein G(o) with calcium channels by the calcium channel beta‐subunit in rat neurones.

The ability of the GABAB agonist (‐) ‐baclofen to inhibit calcium channel currents in cultured rat dorsal root ganglion neurones following depletion of beta‐subunit immunoreactivity is examined to suggest it may function as a GTPase‐activating protein to reduce the ability of activated G(o) to associate with the calcium channel, and thus limit the efficacy of agonists such as (‐).