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DPP6 binds KCND2. 34 / 35
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"From co-IP, we found that PTZ-induced seizure reduced Kv4.2-DPP6 binding in the mouse brain (Fig.  xref )."
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"Taken together, our data demonstrate that Pin1 regulates the composition of the Kv4.2-DPP6 complex and neuronal excitability."
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"However, Kv4.2-DPP6 dissociation by PTZ-induced seizure was abolished in Kv4.2TA mice (Fig.  xref )."
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"Taken together, our results reveal that disrupting the activity-dependent isomerization of Kv4.2 by Pin1 stabilizes the Kv4.2-DPP6 complex and improves cognitive flexibility."
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"Our biochemistry data showed that Kv4.2-DPP6 dissociation is impaired in Kv4.2TA mice, indicating that the Kv4.2-DPP6 complex is more stable without phosphorylation at T607."
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"Using biochemical and electrophysiological techniques, we showed that Pin1 activity is required for the dissociation of the Kv4.2-DPP6 complex and this action alters neuronal excitability."
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"Since the Kv4.2-DPP6 complex is mis-regulated in Kv4.2TA mice (Fig.  xref ), we anticipated disruption of Pin1-Kv4.2 interaction would alter I A . To test this, we performed voltage-clamp recordings from outside-out patches pulled from CA1 pyramidal somata."
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"Thus, the regulation of the Kv4.2-DPP6 complex may not only affect Kv4.2 channel activity but also influence Kv4.2-independent functions of DPP6."
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"Stabilization of the Kv4.2-DPP6 complex might represent a promising strategy for enhancing adaptive cognitive behavior and correcting maladaptive cognitive deficits in a number of neuropsychiatric conditions."
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"P38-Pin1-Kv4.2 pathway regulates Kv4.2-DPP6 complex formation."
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"Considering that both Kv4.2 and DPP6 are implicated in such psychiatric disorders xref , xref , xref , the stability of the Kv4.2-DPP6 complex might be a common factor of pathophysiology."
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"The present study describes a Pin1 isomerase-dependent mechanism that regulates the composition of the Kv4.2-DPP6 complex, neuronal excitability, and cognitive flexibility (Fig.  xref )."
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"This Kv4.2-DPP6 complex dissociation was blocked by the p38 inhibitor SB203580, but not the MEK inhibitor SL327 (Fig.  xref ), suggesting that p38 is required for the dissociation of the Kv4.2-DPP6 complex."
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"As PTZ-induced seizure enhanced Kv4.2 phosphorylation at T607 by p38 (Figs.  xref xref ), we sought to determine if this seizure model also alters Kv4.2-DPP6 binding."
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"Indeed, in the context of the regulation of DPP6-Kv4.2 dynamics, p38 activity in the apical dendrites may be of particular significance."
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"Previous work demonstrated that DPPX tightly binds to Kv4.2, but not Kv3.1, proteins ()."
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"Furthermore, the PTZ-induced Kv4.2-DPP6 complex dissociation was blocked by the Pin1 inhibitor Juglone (Fig.  xref )."
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"We have reported previously, using a heterologous expression system, that the intracellular N-terminal and transmembrane regions of DPP6 associate with Kv4.2 and accelerate channel kinetics."
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"Subtle changes in extracellular pH might modulate the interaction of DPPX with Kv4.2 and possibly with other proteins."
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"This data supports the notion that both Kv4.2 phosphorylation at T607 and Pin1 activity regulate Kv4.2-DPP6 complex formation."
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"We next examined if the regulation of Kv4.2-DPP6 binding is altered in Kv4.2TA mice."
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"The mechanism how Pin1-elicited Kv4.2 conformation change leads to Kv4.2-DPP6 disassociation is interesting and needs to be elucidated in follow up studies."
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"The basal level of Kv4.2-DPP6 protein complex seems unaltered in Kv4.2TA mice compared to WT littermates in biochemistry experiments (Fig.  xref ) whereas we found reduced neuronal excitability in Kv4.2TA mice (Fig.  xref )."
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"KChIP4a, which negatively affects the impact of other KChIPs on Kv4.2, also inhibits the effects of DPPXS, consistent with the formation of a ternary complex of Kv4.2, DPPX-S and KChIPs early in channel biosynthesis."
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No evidence text available
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"In the present study, we report a Pin1-dependent mechanism that regulates the composition of the Kv4.2-DPP6 complex, neuronal excitability and cognitive flexibility."
32218435
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"We wondered if the Kv4.2-DPP6 complex is regulated by Kv4.2 phosphorylation and Pin1 activity."
32218435
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"These data suggest that Pin1 activity is required for the dissociation of the Kv4.2-DPP6 complex in response to neuronal activity."
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"Importantly, we also found that p38-Pin1-Kv4.2 pathway regulates Kv4.2-DPP6 complex (Fig.  xref ) and neuronal excitability (Fig.  xref )."
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"CA1 pyramidal neurons of the hippocampus from these mice exhibited altered Kv4.2-DPP6 interaction, increased A-type K + current, and reduced neuronal excitability."
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"The basal level of Kv4.2-DPP6 protein complex is not altered in Kv4.2TA mice compared to WT littermates in biochemistry experiments (Fig.  xref )."
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"In cultured mouse neurons, synaptic stimulation with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA, 50 µM) for 15 min resulted in decreased Kv4.2-DPP6 binding, which was opposed by the expression of PinC113S, an isomerase dead mutant (Fig.  xref )."
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"We show that activity-induced Kv4.2 phosphorylation triggers Pin1 binding to, and isomerization of, Kv4.2 at the pThr 607 -Pro motif, leading to the dissociation of the Kv4.2-DPP6 complex."
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No evidence text available
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