IndraLab

Statements


| 1 35

sparser
"Unlike the well-studied interaction between GluN2B and PSD-95, the Kv2.1syntaxin interaction was not molecularly localized on the target protein."
| PMC

sparser
"The Kv2.1syntaxin interaction appears to not be necessary for the basal trafficking of the Kv2.1 channel."
| PMC

sparser
"This is the first in vivo evidence that targeting the Kv2.1syntaxin interaction can be neuroprotective, as it has been shown many times previously in in vitro models."
| PMC

sparser
"Others have sought to identify agents targeting the surge mechanism, which relies on the interaction between the C-terminus of KCNB1 and syntaxin."

sparser
"Here, we show that Kv2.1-induced facilitation of release is not restricted to neuroendocrine cells, but also occurs in the somatic-vesicle release from dorsal-root-ganglion neurons and is mediated by direct association of Kv2.1 with syntaxin."

sparser
"We showed previously that the observed increase in K(+) currents is a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-mediated process, and that the SNARE protein syntaxin binds directly to Kv2.1 channels."

sparser
"In the present study, we tested whether disrupting the interaction of Kv2.1 and syntaxin promoted the survival of cortical neurons following injury."

sparser
"These results establish that binding of syntaxin to Kv2.1 is crucial for the manifestation of oxidant-induced apoptosis, and thereby reveal a potential new direction for therapeutic intervention in the treatment of neurodegenerative disorders."

sparser
"Importantly, the physical interaction of Kv2.1 with syntaxin was shown to be involved in the facilitation of secretion from PC12 cells, which was independent of potassium currents."

sparser
"Thus, direct association of Kv2.1 with syntaxin promotes exocytosis."

sparser
"Similarly the voltage sensitive potassium channel Kv2.1 can also interact with syntaxin 1 ( xref , xref )."

sparser
"We show that impairment of the interaction of syntaxin with endogenous Kv2.1 attenuates NE release."

sparser
"The interaction of Kv2.1 with syntaxin and its insertion in the plasma membrane upon oxidative stress signals also requires the action of CamKII."

sparser
"Interestingly, targeting the Kv2.1-syntaxin interaction with a peptide mimicking the syntaxin-1A binding domain of Kv2.1 ameliorated cell death in an in vivo model of ischemic stroke ( xref )."

sparser
"Here a rational approach was applied to define the key molecular interactions between syntaxin and Kv2.1, some of which are shared with mammalian uncoordinated-18 (munc18)."

sparser
"Firstly, in view of the proposal that syntaxin lines the fusion pore xref , the Kv2.1-syntaxin interaction may promote full collapse fusion, which induces complete release, in place of the incomplete release associated with kiss and run exocytosis."

sparser
"Secondly, in view of the demonstration that Kv2.1 preferentially binds the open conformation of syntaxin xref , the Kv2.1-syntaxin interaction may influence the equilibrium between the closed and open conformations of syntaxin."

sparser
"Thirdly, the Kv2.1-syntaxin interaction may influence the equilibrium between the reserve and the releasable pools of vesicles."

sparser
"In any of these or other possible mechanisms, both our studies together provide strong evidence that the Kv2.1-syntaxin interaction exerts its effect on secretion after ATP-dependent priming of the vesicles."

sparser
"Given the proposed role for surface VAMP2 in the regulation of the vesicle cycle and the important role for the sustained Kv2.1 current in the regulation of dendritic calcium entry during high-frequency stimulation, the interaction of VAMP2 with Kv2.1 N terminus may contribute, alongside with the interaction of syntaxin with Kv2.1 C terminus, to the activity dependence of DCV release."

sparser
"Previous preclinical studies from our laboratory have shown efficacious neuroprotection in vivo by targeting the Kv2.1-syntaxin interaction (fig."
| PMC

sparser
"Strong evidence from Ilana Lotan’s lab has suggested that, in a manner independent of K + flow, Kv2.1 directly interacts with syntaxin in facilitating exocytosis, further substantiating the presence of non-canonical functions of Kv channels ( xref )."

reach
"This effort has led to the identification of a small molecule inhibitor (cpd5) of the protein–protein interaction between syntaxin and KCNB1, that has shown some efficacy in ameliorating neuronal loss in middle cerebral artery occlusion mouse model of ischemic stroke [121]."

sparser
"Disrupting the Kv2.1Syntaxin Interaction."
| PMC

sparser
"These channel modification events increase the interaction between Kv2.1 and syntaxin that is seemingly solely necessary for apoptotic trafficking of the channel [ xref ]."
| PMC

sparser
"In a bid to further understand the Kv2.1syntaxin interaction and to extend the effectiveness of our approach, we utilized molecular dynamic simulations to dock C1aB onto syntaxin [ xref ]."
| PMC

sparser
"We localized the Kv2.1syntaxin interaction to a highly coordinated binding pocket centered on the syntaxin Ha helix."
| PMC

sparser
"This effort has led to the identification of a small molecule inhibitor (cpd5) of the protein–protein interaction between syntaxin and KCNB1, that has shown some efficacy in ameliorating neuronal loss in middle cerebral artery occlusion mouse model of ischemic stroke [ xref ]."

sparser
"Thus, we postulated that direct association of overexpressed Kv2.1 with syntaxin promotes exocytosis."

sparser
"Moreover, we show that impairment of the syntaxin-Kv2.1 interaction during the triggering phase is responsible for the reduced release."

sparser
"Here, we further characterized the binding of native syntaxin from PC12 cells to the Kv2.1 peptides."

sparser
"Next, in an effort to evaluate the involvement of the interaction between endogenous Kv2.1 and syntaxin in the Ca 2+ -regulated secretion from PC12 cells, we aimed to disrupt this interaction and to assay the impact on secretion."

sparser
"The above Kv2.1-derived syntaxin-binding peptides were shown to compete for the in situ association of syntaxin with Kv2.1 in PC12 cells xref and, hence, were suited for this purpose."

sparser
"This study is a direct continuation of and complement to our previous study xref ; both studies strongly suggest that Kv2.1-syntaxin interaction causes an enhancement of the release of DCVs."

sparser
"Notably, in both studies, the impact of the Kv2.1-syntaxin interaction on secretion was studied under conditions in which K + ion efflux and membrane potential changes were either minimal (secretion from living cells elicited by increasing the extracellular K + concentration ; xref or irrelevant (secretion from cells with permeable plasma membranes; this study)."

sparser
"Thus, the impact of Kv2.1-syntaxin interaction does not result from a change in the voltage-dependent gating of the channel, but rather reflects the effect of a direct interaction between the channel and the secretory machinery"