IndraLab

Statements


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sparser
"Because the binding of Hax-1 to Kv3.3 prevents rapid inactivation of the channels xref , we tested the effects of the TBK1 inhibitor on the characteristics of Kv3.3 currents using the whole-cell patch-clamp technique."

sparser
"These findings are consistent with the hypothesis that TBK1-dependent association of Kv3.3 with Hax-1 regulates its rate of inactivation (Fig.  xref ) and the finding that inactivation of G592R Kv3.3 channels is slower than that of wild type channels (Fig.  xref )."

sparser
"The binding of Hax-1 to the C-terminus of Kv3.3 channels also prevents rapid inactivation of the channel during depolarization."

reach
"Accordingly, the binding of Hax-1 to Kv3.3 directly triggers the formation of a stable channel-associated subcortical actin cytoskeleton that acts to prevent inactivation of Kv3.3 during depolarization [8]."

reach
"A recent study has shown that the cytoplasmic C-terminal domain of Kv3.3 channels binds Hax-1, an anti-apoptotic protein required for the survival of cerebellar neurons [8]."

reach
"Presynaptic stabilisation of Kv3.3 however, is unlikely to be through ankyrin-R alone, as this mechanism would not discriminate between the subunits.Another possibility is that Kv3.3 inactivation is suppressed by the C-terminus associating with Hax1 (Blosa et al., 2015) to bind the Kv3.3 N-Terminal ball peptide and modulate the actin network."

sparser
"TBK1 activity is required for the binding of Kv3.3 to its auxiliary subunit Hax-1, which prevents channel inactivation."

sparser
"Although the precise molecular details of the interactions remain to be established, a simple working model would have the C terminus of Kv3.3 interacting directly with Hax-1, leading to Rac-mediated [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Accordingly, the binding of Hax-1 to Kv3.3 directly triggers the formation of a stable channel-associated subcortical actin cytoskeleton that acts to prevent inactivation of Kv3.3 during depolarization [ xref ]."

reach
"The Kv3.3 channel directly binds Hax-1, a cell survival protein."

sparser
"The effects of Kv3.3 on the actin cytoskeleton are mediated by the binding of the cytoplasmic C-terminus of Kv3.3 to Hax-1, an anti-apoptotic protein that regulates actin nucleation through Arp2/3."

sparser
"The binding of Hax-1 to Kv3.3 is also required to prevent the channel from inactivating rapidly during sustained depolarization xref ."

sparser
"TBK1 activity is required for the binding of Kv3.3 to its auxiliary subunit Hax-1, which prevents channel inactivation with depolarization."

sparser
"Here, the authors show that the known Kv3.3 channel complex with Hax1, which affects spinal cerebellar ataxia, regulates the enzyme Tank Binding Kinase 1, modulating survival of cerebellar neurons."

sparser
"Thus, the interaction of Kv3.3 with Hax-1 leads to formation of a stable subcortical actin cytoskeleton under the plasma membrane where Kv3.3 is expressed."

sparser
"On the other hand, TBK1 activity is required for Kv3.3 to bind to its auxiliary subunit Hax-1, preventing channel inactivation."

sparser
"To probe further how an abnormal interaction between Kv3.3 and Hax-1 leads to cerebellar degeneration, we used CRISPR/Cas9 gene editing to generate homozygous G592R Kv3.3 knock-in mice (Supplementary Fig.  xref )."

reach
"It results in the degradation of a cell survival protein (Hax-1) that binds to Kv3.3 directly [63]."