"SCA13 (prevalence : < 1/1000,000) is caused by point mutations in the KCNC3 gene (encoding K v 3.3 channels), which affect channel function by gain- and loss-of-function mechanisms."
"Therefore, we conclude that we have identified at least one novel pathogenic mutation in KCNC3 that cause SCA13 and two additionally potential SCA13 mutations."
"Although Hax-1 binds G592R Kv3.3, its ability to trigger Arp2/3-dependent actin nucleation and to link N-type inactivation to the cytoskeleton is impaired when bound to this mutant channel."
"The interaction between Kv3.3 and Hax-1 provides potential links between SCA13 mutations and degeneration of neurons such as cerebellar Purkinje cells."
"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."
"Moreover, effects of cortical Kv3.3-Hax-1 interactions are likely to be abolished in disease-causing mutations that prevent trafficking of Kv3.3 to the plasma membrane ( Gallego-Iradi et al., 2014 )."
"Elimination of the first 78 amino acids of the N terminus of Kv3.3 produced noninactivating currents suggesting that PKC modulates N-type inactivation, potentially by phosphorylation of sites in this region."
"Computer simulations of model neurons suggest that phosphorylation of Kv3.3 by PKC may allow neurons to maintain action potential height during stimulation at high frequencies, and may therefore contribute to stimulus-induced changes in the intrinsic excitability of neurons such as those of the auditory brainstem."
"Computer simulations of model neurons suggest that phosphorylation of Kv3.3 by PKC may allow neurons to maintain action potential height during stimulation at high frequencies, and may therefore contribute to stimulus-induced changes in the intrinsic excitability of neurons such as those of the auditory brainstem."
"Elimination of the first 78 amino acids of the N terminus of Kv3.3 produced noninactivating currents suggesting that PKC modulates N-type inactivation, potentially by phosphorylation of sites in this region. To identify potential phosphorylation sites, we investigated the response of channels in which serines in this N-terminal domain were subjected to mutagenesis. Our results suggest that serines at positions 3 and 9 are potential PKC phosphorylation sites."
"In fact, SynDIG4 appeared to preferentially interact with the voltage-gated potassium channel subunits KCNC1 and KCNC3 and the post-synaptic scaffolding protein Homer3 in the cerebellum."
"A rare form of dominantly inherited ataxia, SCA13 is caused by mutations in the KCNC3 gene encoding the voltage gated potassium channel protein, Kv3.3."
"Sectioning these eyes to uncover the arrangement of photoreceptor cells within each ommatidium revealed that expression of LacZ or KCNC3 WT did not perturb the differentiation or organization of the photoreceptor cells (XREF_FIG, bottom row)."
"For example, some forms of SCA, such as SCA13, SCA14 and SCA28 [ xref ; xref ; xref ; xref ], begin in childhood and/or early adult life, progress very slowly and may be associated with a normal lifespan."
"For example, some forms of SCA, such as SCA13, SCA14 and SCA28 [ xref ; xref ; xref ; xref ], begin in childhood and/or early adult life, progress very slowly and may be associated with a normal lifespan."
"Negative co-immunoprecipitation data confirms that the intracellular retention of EGFR by KCNC3 R423H is not likely to be dependent on a direct protein-to-protein interactions."
"To test whether the interaction of Kv3.3 with Arp2/3 influences actin nucleation, we carried out triple channel confocal imaging of actin filaments, Arp2/3, and the Kv3.3 channel in untransfected CHO cells and in cells transiently or stably expressing wild-type Kv3.3 ( Figures 1 B–1E and S1 A)."
"In expression systems, the channels produced by the expression of Kcnc1 and Kcnc2 produce delayed rectifier K + currents, whereas the expression of Kcnc3 and Kcnc4 produce inactivating A-type K + currents."
"In fact, SynDIG4 appeared to preferentially interact with the voltage-gated potassium channel subunits KCNC1 and KCNC3 and the post-synaptic scaffolding protein Homer3 in the cerebellum."
"► Kv3.1b and Kv3.3 expression was studied in dorsal horn GABAergic interneurones. ► Kv3.1b or Kv3.3 was most abundantly expressed in laminae I–III. ► Kv3.1b but not Kv3.3 was associated with GAD65 and GAD67 neurones. ► Capsaicin-induced c-fos expression was localized mainly to GAD65-GFP interneurones."
"Because the profound KCNC3 R423H eye phenotype can be almost completely rescued by elevated Egfr expression and R423H and Egfr-RNAi co-expression accentuates wing malformations, a direct or indirect association is strongly implicated between KCNC3 and Egfr, as well as a link between this potent growth factor receptor and cerebellar hypoplasia."
"Similarly, KCNC3 R423H self-cross, driven by dpp-Gal4 in the wing, led to disruption of veins L2, L3, and ACV in the wing (XREF_FIG compared to XREF_FIG), whereas co-expression of KCNC3 WT with KCNC3 R423H resulted in a phenotype similar to KCNC3 R423H alone (XREF_FIG compared to XREF_FIG)."
"To test whether the interaction of Kv3.3 with Arp2/3 influences actin nucleation, we carried out triple channel confocal imaging of actin filaments, Arp2/3, and the Kv3.3 channel in untransfected CHO cells and in cells transiently or stably expressing wild-type Kv3.3 ( Figures 1 B–1E and S1 A)."