Functional interactions between presynaptic calcium channels and the neurotransmitter release machinery

Spafford, J. David; Zamponi, Gerald W.

doi:10.1016/s0959-4388(03)00061-8

Cited by 111 publications

(76 citation statements)

References 52 publications

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“…The SNARE-binding region of calcium channels has been shown to bind the target SNAREs syntaxin and SNAP-25 and the vesicular SNARE synaptotagmin (11). The binding of syntaxin to the channel is important for stabilization of the binding of G␤␥ subunits (12). Our results suggest that a tyrosine-based motif within the synprint region (centered about Tyr-804) plays an important role in determining the rate of desensitization of GABA-mediated voltage-independent inhibition.…”

mentioning

confidence: 66%

RGS12 Interacts with the SNARE-binding Region of the Cav2.2 Calcium Channel

Richman

Strock

Hains

et al. 2005

Journal of Biological Chemistry

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Activation of GABA B receptors in chick dorsal root ganglion (DRG) neurons inhibits the Ca v 2.2 calcium channel in both a voltage-dependent and voltage-independent manner. The voltage-independent inhibition requires activation of a tyrosine kinase that phosphorylates the ␣ 1 subunit of the channel and thereby recruits RGS12, a member of the "regulator of G protein signaling" (RGS) proteins. Here we report that RGS12 binds to the SNARE-binding or "synprint" region (amino acids 726 -985) in loop II-III of the calcium channel ␣1 subunit. A recombinant protein encompassing the Nterminal PTB domain of RGS12 binds to the synprint region in protein overlay and surface plasmon resonance binding assays; this interaction is dependent on tyrosine phosphorylation and yet is within a sequence that differs from the canonical NPXY motif targeted by other PTB domains. In electrophysiological experiments, microinjection of DRG neurons with synprint-derived peptides containing the tyrosine residue Tyr-804 altered the rate of desensitization of neurotransmitter-mediated inhibition of the Ca v 2.2 calcium channel, whereas peptides centered about a second tyrosine residue, Tyr-815, were without effect. RGS12 from a DRG neuron lysate was precipitated using synprint peptides containing phosphorylated Tyr-804. The high degree of conservation of Tyr-804 in the SNAREbinding region of Ca v 2.1 and Ca v 2.2 calcium channels suggests that this region, in addition to the binding of SNARE proteins, is also important for determining the time course of the modulation of calcium current via tyrosine phosphorylation.Multiple G protein-mediated signaling pathways are known to modulate Ca v 2.2 (N-type) calcium channels (1, 2) via direct G protein-ion channel interactions, activation of second messenger cascades, and activation of tyrosine kinases (3, 4). This modulation of voltage-dependent calcium channels is a transient phenomenon. Upon prolonged exposure to a neurotransmitter, neurons become unresponsive or desensitized. Despite the common requirement for the activation of a G proteincoupled receptor kinase (GRK3) for desensitization of the neurotransmitter-mediated inhibition of calcium current (5), G i -and G o -mediated pathways exhibit different rates of desensitization (6) that may result from selective effects of the G␣-directed GTPase-accelerating activity borne by "regulator of G protein signaling" (RGS) 1 proteins (7,8).In dorsal root ganglion (DRG) neurons, the activation of ␥-aminobutyric acid type B (GABA B ) receptors induces both voltage-dependent and voltage-independent inhibition of Ca v 2.2 channels (9). Voltage-independent inhibition requires the activation of a tyrosine kinase that phosphorylates the pore-forming ␣-subunit of the calcium channel (10). The tyrosine-phosphorylated form of the ␣-subunit becomes a target for the phosphotyrosine binding (PTB) domain of RGS12, a member of the RGS protein superfamily that specifically accelerates the rate of desensitization of this response (10).To better understand the molecular b...

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mentioning

confidence: 66%

RGS12 Interacts with the SNARE-binding Region of the Cav2.2 Calcium Channel

Richman

Strock

Hains

et al. 2005

Journal of Biological Chemistry

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“…Previous reports have demonstrated functional impacts of syntaxin, SNAP-25, and synaptotagmin on VDCCs through their physical association with the "synprint" region in the II-III linker of ␣ 1 -proteins (9,19,22). It has also been reported that RIM1 and RIM2 associate with the synprint (38,69) directly via the C 2 A domain and with the ␣ 1 C-terminal tail indirectly via the RIM-BP (70) (Fig.…”

Section: Discussionmentioning

confidence: 90%

Rab3-interacting Molecule γ Isoforms Lacking the Rab3-binding Domain Induce Long Lasting Currents but Block Neurotransmitter Vesicle Anchoring in Voltage-dependent P/Q-type Ca2+ Channels

Uriu

Kiyonaka

Miki

et al. 2010

Journal of Biological Chemistry

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“…This type of channel is a major regulator of cytosolic calcium (Dolphin, 1998;Catterall, 2000) and therefore has important implications for neuronal physiology (West et al, 2002;Spafford and Zamponi, 2003). The present study was designed to look for a functional link between these two GTPase-associated mechanisms using the chick ciliary neuron, which abundantly expresses both N-cadherin and high-threshold voltage-activated (HVA) calcium channels of the N type (White et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

N-Cadherin Juxtamembrane Domain Modulates Voltage-Gated Ca²⁺Current via RhoA GTPase and Rho-Associated Kinase

Piccoli¹,

Rutishauser²,

Brusés³

2004

J. Neurosci.

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The juxtamembrane domain (JMD) of N-cadherin cytoplasmic tail is an important regulatory region of the clustering and adhesion activities of the protein. In addition, the JMD binds a diversity of proteins capable of modifying intracellular processes including cytoskeletal rearrangement mediated by Rho GTPases. These GTPases also function as regulators of voltage-activated calcium channels, which in turn modulate neuronal excitability. The present study was designed to determine whether there is a direct functional link, via Rho GTPase, between the N-cadherin JMD and these voltage-activated channels. It was found that the infusion of the soluble JMD into chick ciliary neurons causes a substantial decrease in the amplitude of the high-threshold voltage-activated (HVA) calcium current. The activation time is increased while the inactivation process is reduced, suggesting that the decreased current amplitude reflects a reduction in the number of channels available to open. This effect was reversed by inhibition of RhoA or its downstream effector, Rho-associated kinase (ROCK). Because ROCK determines the active state of myosin, these results suggest that the modulation of HVA by the JMD could be mediated by changes in the status of the actin-myosin cytoskeleton.

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Functional interactions between presynaptic calcium channels and the neurotransmitter release machinery

Cited by 111 publications

References 52 publications

RGS12 Interacts with the SNARE-binding Region of the Cav2.2 Calcium Channel

RGS12 Interacts with the SNARE-binding Region of the Cav2.2 Calcium Channel

Rab3-interacting Molecule γ Isoforms Lacking the Rab3-binding Domain Induce Long Lasting Currents but Block Neurotransmitter Vesicle Anchoring in Voltage-dependent P/Q-type Ca2+ Channels

N-Cadherin Juxtamembrane Domain Modulates Voltage-Gated Ca²⁺Current via RhoA GTPase and Rho-Associated Kinase

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Functional interactions between presynaptic calcium channels and the neurotransmitter release machinery

Cited by 111 publications

References 52 publications

RGS12 Interacts with the SNARE-binding Region of the Cav2.2 Calcium Channel

RGS12 Interacts with the SNARE-binding Region of the Cav2.2 Calcium Channel

Rab3-interacting Molecule γ Isoforms Lacking the Rab3-binding Domain Induce Long Lasting Currents but Block Neurotransmitter Vesicle Anchoring in Voltage-dependent P/Q-type Ca2+ Channels

N-Cadherin Juxtamembrane Domain Modulates Voltage-Gated Ca2+Current via RhoA GTPase and Rho-Associated Kinase

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N-Cadherin Juxtamembrane Domain Modulates Voltage-Gated Ca²⁺Current via RhoA GTPase and Rho-Associated Kinase