IndraLab

Statements

PEX5L inhibits HCN1. 17 / 17
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"These results imply that a reduction in TRIP8b expression produces a defect in HCN1 membrane trafficking."
21555075
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"Exon 4 is also found in the TRIP8b (1b-2-4) splice variant, which has been reported to decrease HCN1 surface localization 15."
33547341
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"Thus, if TRIP8b inhibits HCN1 gating by antagonizing the facilitatory action of basal levels of cAMP, then we expect that the gating of the two mutant channels should be unaffected by the presence of TRIP8b."
19555649
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"As expected, the presence of TRIP8b significantly reduced the time constants of HCN1 current activation, while accelerating the time constant of deactivation (XREF_FIG and XREF_TABLE)."
32633755
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"Conversely, selective disruption of the downstream interaction site, either by introducing the N to K mutation in the TRIP8b (1a-4) TPR domain or by ablating the TPR domain in the TRIP8b (1a-4) DeltaTPR construct, had essentially no effect on the ability of TRIP8b to inhibit HCN1 gating (XREF_FIG)."
21411649
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"As TRIP8b DeltaNterm can bind efficiently to HCN1 at the downstream SNL and TPR interaction site but can not bind to HCN channels at the upstream C-linker and CNBD site, the upstream interaction must be critical for the TRIP8b dependent inhibition of HCN1 channel opening."
21411649
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"Furthermore, TRIP8b can inhibit the axonal distribution of HCN1 in the medial perforant path XREF_BIBR."
24409334
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"Thus, the effect of TRIP8b (1a) to downregulate HCN1 requires a dileucine based trafficking motif in exon 5 whereas channel downregulation with TRIP8b (1b-2) depends on a tyrosine based trafficking motif in exon 2."
21411649
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"As downregulation of TRIP8b with siRNA decreases HCN1 surface expression, the HCN1 DeltaSNL results further indicate that the actions of TRIP8b to enable proper surface membrane expression and direct distal dendritic targeting of HCN1 are dissociable functions."
21555075
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"In a previous study, our laboratory found that the action of TRIP8b to antagonize the cAMP dependent shift in HCN1 voltage gating observed in intact cells was greatly diminished upon patch excision when TRIP8b and HCN1 were expressed independently, perhaps because of instability of the complex and/or loss of some intracellular modulatory factor."
24277603
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"TRIP8b inhibits HCN1 channel opening."
19555649
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"Trip8b inhibits HCN1 by reducing its sensitivity to cAMP and the efficacy by which cAMP opens the channel."
28057841
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"TRIP8b (1b-2) and TRIP8b (1b-2-4) cause a near complete loss of surface expression; TRIP8b (1a) causes a smaller but still marked ~ 10-fold decrease in HCN1 current density; TRIP8b (1a-2) has no effect on surface expression; and TRIP8b (1a-4) and TRIP8b (1a-2-4) cause up to a ~ 6-fold increase in surface expression."
19555649
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"TRIP8b isoforms could up- or down-regulate HCN1 mediated I h by altering the channel conductance or by changing the number of channels expressed on the cell surface."
19439603
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"Although the near complete downregulation of HCN1 current with TRIP8b (1b-2) prevented us from examining its effects on channel gating, the TRIP8b (1b-2) Y38A and L41A exon 2 mutant, which does not downregulate HCN1, also exerts a hyperpolarizing shift in HCN1 gating."
19555649
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"Indeed, the internal deletion abolished the ability of TRIP8b (1a-4) to inhibit HCN1 gating (XREF_FIG), confirming the importance of the upstream CNBD and core interaction in regulating channel opening."
21411649
sparser
"The simplest interpretation of these results is that TRIP8b does indeed inhibit HCN1 gating by antagonizing the actions of basal levels of cAMP."
19555649