The 25-kDa Synaptosome-associated Protein (SNAP-25) Binds and Inhibits Delayed Rectifier Potassium Channels in Secretory Cells

Ji, Junzhi; Tsuk, Sharon; Salapatek, Anne Marie; Huang, Xiaohang; Chikvashvili, Dodo; Pasyk, Ewa A.; Kang, Youhou; Sheu, Laura; Tsushima, Robert G.; Diamant, Nicholas E.; Trimble, William S.; Lotan, Ilana; Gaisano, Herbert Y.

doi:10.1074/jbc.m201034200

Cited by 42 publications

(37 citation statements)

References 51 publications

(65 reference statements)

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“…It is recognised that voltage-dependent outward K + currents in insulin secreting cells are comprised of both Ca 2+ -dependent (K Ca ) and a Ca 2+ -independent (Kv) current components. Studies by us and others suggest that the Kv and K Ca components contribute 80 to 85% and 15 to 20% of total voltage-dependent outward currents respectively [3,74,83]. Single Kv and K Ca channels have also been resolved in insulinoma (HIT) cells [84] and mouse beta cells [72,74].…”

Section: Electrophysiological Evidence For Different Repolarising Curmentioning

confidence: 99%

“…This is, in part, due to the lack of appropriate pharmacological and/or molecular agents. Studies with the limited number of Kv1 antagonists suggest little contribution from this family [52,83], although Kv1.1 might contribute somewhat in the HIT-T15 insulinoma cell line [83]. The ability of these antagonists to block heterotetrameric channels is not known, however.…”

Section: Electrophysiological Evidence For Different Repolarising Curmentioning

confidence: 99%

“…It is now becoming clear that, while the SNARE complex mediates the molecular events of exocytosis upon elevation of [Ca 2+ ] i , it is also functionally coupled to the excitatory machinery in a unit termed the 'excitosome'. This hypothesis results largely from studies showing that SNARE proteins can associate with and regulate VDCCs [83,131,132,133].…”

Section: Regulation Of Kv Channel Activity In Beta Cellsmentioning

confidence: 99%

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Voltage-dependent K + channels in pancreatic beta cells: Role, regulation and potential as therapeutic targets

2003

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Insulin secretion from pancreatic islet beta cells is acutely regulated by a complex interplay of metabolic and electrogenic events. The electrogenic mechanism regulating insulin secretion from beta cells is commonly referred to as the ATP-sensitive K + (K ATP ) channel dependent pathway. Briefly, an increase in ATP and, perhaps more importantly, a decrease in ADP stimulated by glucose metabolism depolarises the beta cell by closing K ATP channels. Membrane depolarisation results in the opening of voltage-dependent Ca 2+ channels, and influx of Ca 2+ is the main trigger for insulin secretion. Repolarisation of pancreatic beta cell action potential is mediated by the activation of voltage-dependent K + (Kv) channels. Various Kv channel homologues have been detected in insulin secreting cells, and recent studies have shown a role for specific Kv channels as modulators of insulin secretion. Here we review the evidence supporting a role for Kv channels in the regulation of insulin secretion and discuss the potential and the limitations for beta-cell Kv channels as therapeutic targets. Furthermore, we review recent investigations of mechanisms regulating Kv channels in beta cells, which suggest that Kv channels are active participants in the regulation of beta-cell electrical activity and insulin secretion. [Diabetologia (2003[Diabetologia ( ) 46:1046[Diabetologia ( -1062

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Section: Electrophysiological Evidence For Different Repolarising Curmentioning

confidence: 99%

Section: Electrophysiological Evidence For Different Repolarising Curmentioning

confidence: 99%

Section: Regulation Of Kv Channel Activity In Beta Cellsmentioning

confidence: 99%

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Voltage-dependent K + channels in pancreatic beta cells: Role, regulation and potential as therapeutic targets

2003

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“…Kv2.1 (kindly donated by O. Pongs, Zentrum fur Molecular Neurobiologie, University of Hamburg, Hamburg, Germany), Syx, and SNAP (kindly donated by E. Isacoff, Berkeley, CA) cDNAs were cloned in pGEMHE. BoNT/A and BoNT/C light chain cDNAs cloned in pCDNA3 have been described previously (22). Preparation of mRNAs was as described (23).…”

Section: Methodsmentioning

confidence: 99%

Direct Interaction of Target SNAREs with the Kv2.1 Channel

Michaelevski¹,

Chikvashvili²,

Tsuk³

et al. 2003

Journal of Biological Chemistry

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Previously we suggested that interaction between voltage-gated K ؉ channels and protein components of the exocytotic machinery regulated transmitter release. This study concerns the interaction between the Kv2.1 channel, the prevalent delayed rectifier K ؉ channel in neuroendocrine and endocrine cells, and syntaxin 1A and SNAP-25. We recently showed in islet ␤-cells that the Kv2.1 K ؉ current is modulated by syntaxin 1A and SNAP-25. Here we demonstrate, using co-immunoprecipitation and immunocytochemistry analyses, the existence of a physical interaction in neuroendocrine cells between Kv2.1 and syntaxin 1A. Furthermore, using concomitant co-immunoprecipitation from plasma membranes and two-electrode voltage clamp analyses in Xenopus oocytes combined with in vitro binding analysis, we characterized the effects of these interactions on the Kv2.1 channel gating pertaining to the assembly/disassembly of the syntaxin 1A/SNAP-25 (target (t)-SNARE) complex. Syntaxin 1A alone binds strongly to Kv2.1 and shifts both activation and inactivation to hyperpolarized potentials. SNAP-25 alone binds weakly to Kv2.1 and probably has no effect by itself. Expression of SNAP-25 together with syntaxin 1A results in the formation of t-SNARE complexes, with consequent elimination of the effects of syntaxin 1A alone on both activation and inactivation. Moreover, inactivation is shifted to the opposite direction, toward depolarized potentials, and its extent and rate are attenuated. Based on these results we suggest that exocytosis in neuroendocrine cells is tuned by the dynamic coupling of the Kv2.1 channel gating to the assembly status of the t-SNARE complex.The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) 1 proteins syntaxin, SNAP-25, and VAMP are crucial factors in processes of transmitter and hormone release (1). They interact with a wide range of proteins, some of them (such as synaptotagmin) associated with vesicular membranes or with plasma membranes (for example, voltage-gated Ca 2ϩ channels) (1-5). We suggested previously (6) that SNARE proteins interact with a member of the Kv1 subfamily of the voltage-gated K ϩ (Kv) channels and that these interactions may play a role in synaptic efficacy and neuronal excitability. Our results showed that in brain synaptosomes the presynaptic Kv1.1 channel (7) interacts with some of the protein components of the exocytotic apparatus, including syntaxin 1A, SNAP-25, and synaptotagmin, in a manner that is sensitive to the exocytotic state of the synaptosomes. We also showed that Kv1.1 in complex with the auxiliary Kv␤ 1.1 subunits (8) interacts directly with syntaxin 1A, and the feedback effect of this interaction on the channel function enhances its fast inactivation in Xenopus oocytes. Involvement of G protein ␤␥ subunits was found to be a requirement for this interaction (9). These characteristics of the interaction of presynaptic Kv channels with syntaxin 1A are reminiscent of the interaction of the presynaptic N-type voltage-gated Ca 2ϩ channels (10 -12)....

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“…We demonstrated that the Kv channel composed of the pore forming Kv1.1 and auxiliary Kv␤ subunits interact in fresh brain synaptosomes with syntaxin 1A, SNAP-25, and synaptotagmin, and this interaction is relieved following triggering of transmitter release. Furthermore, in insulinoma HIT-T15 ␤ cells the activity of Kv1.1 channel was inhibited by SNAP-25 (5). Also, we showed, in Xenopus oocytes, that the direct interaction of the Kv1.1/Kv␤1.1 (␣␤) channel with syntaxin 1A enhances the fast inactivation of the channel (4) that is conferred by the N-terminal part of ␤, in a mechanism termed "ball and chain" inactivation (6).…”

mentioning

confidence: 82%

Modulation of a Brain Voltage-gated K+ Channel by Syntaxin 1A Requires the Physical Interaction of Gβγ with the Channel

Michaelevski

Chikvashvili

Tsuk

et al. 2002

Journal of Biological Chemistry

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Recently we suggested that direct interactions between voltage-gated K؉ channels and proteins of the exocytotic machinery, such as those observed between the Kv1.1/Kv␤ channel, syntaxin 1A, and SNAP-25 may be involved in neurotransmitter release. Furthermore, we demonstrated that the direct interaction with syntaxin 1A enhances the fast inactivation of Kv1.1/Kv␤1.1 in oocytes. Here we show that G-protein ␤␥ subunits play a crucial role in the enhancement of inactivation by syntaxin 1A. The effect caused by overexpression of syntaxin 1A is eliminated in the presence of chelators of endogenous ␤␥ subunits in the whole cell and at the plasma membrane. Conversely, enhancement of inactivation caused by overexpression of ␤ 1 ␥ 2 subunits is eliminated upon knock-down of endogenous syntaxin or its scavenging at the plasma membrane. We further show that the N terminus of Kv1.1 binds brain synaptosomal and recombinant syntaxin 1A and concomitantly binds ␤ 1 ␥ 2 ; the binding of ␤ 1 ␥ 2 enhances that of syntaxin 1A. Taken together, we suggest a mechanism whereby syntaxin and G protein ␤␥ subunits interact concomitantly with a Kv channel to regulate its inactivation.Voltage-gated K ϩ (Kv) 1 channels participate in a host of cellular processes, from setting the resting membrane potential and shaping action potential wave-form and frequency to controlling synaptic strength (1). Recently, we challenged the commonly accepted concept that presynaptic Kv channels participate in neurotransmitter release simply by virtue of their ability to shape action potentials that invade nerve terminals (2, 3), and suggested that the fine tuning of transmitter release might be attributable to direct interaction between Kv channels and proteins of the exocytotic machinery (4). We demonstrated that the Kv channel composed of the pore forming Kv1.1 and auxiliary Kv␤ subunits interact in fresh brain synaptosomes with syntaxin 1A, SNAP-25, and synaptotagmin, and this interaction is relieved following triggering of transmitter release. Furthermore, in insulinoma HIT-T15 ␤ cells the activity of Kv1.1 channel was inhibited by SNAP-25 (5). Also, we showed, in Xenopus oocytes, that the direct interaction of the Kv1.1/Kv␤1.1 (␣␤) channel with syntaxin 1A enhances the fast inactivation of the channel (4) that is conferred by the N-terminal part of ␤, in a mechanism termed "ball and chain" inactivation (6). The reciprocal effects of ␣, syntaxin 1A, and SNAP-25 are reminiscent of the finding that presynaptic Nand L-type voltage-gated Ca 2ϩ channels interact directly with proteins of the exocytotic apparatus in neurons, and that their interaction with syntaxin 1A and SNAP-25 causes feedback effects on the channel function in oocytes (reviewed in Ref . 7) and in synaptosomes (8). Recent studies have shown that disruption of the interaction with syntaxin 1A in neurons has functional implications for transmitter release, reducing the efficacy of both Ca 2ϩ -dependent (7, 9) and Ca 2ϩ -independent (10) release.Previous studies by our group have shown that the e...

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The 25-kDa Synaptosome-associated Protein (SNAP-25) Binds and Inhibits Delayed Rectifier Potassium Channels in Secretory Cells

Cited by 42 publications

References 51 publications

Voltage-dependent K + channels in pancreatic beta cells: Role, regulation and potential as therapeutic targets

Voltage-dependent K + channels in pancreatic beta cells: Role, regulation and potential as therapeutic targets

Direct Interaction of Target SNAREs with the Kv2.1 Channel

Modulation of a Brain Voltage-gated K+ Channel by Syntaxin 1A Requires the Physical Interaction of Gβγ with the Channel

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