IndraLab

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PEX5L decreases the amount of HCN1. 23 / 23
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"As mentioned above, these isoforms exert distinct effects on HCN1 trafficking : TRIP8b (1a-4) strongly increases HCN1 surface expression; TRIP8b (1a) produces a ~ 10 fold decrease of HCN1 surface expression in Xenopus oocytes but enhances HCN1 expression in a mammalian cell line; and TRIP8b (1b-2) essentially abolishes surface expression in both oocytes and mammalian cells (> 50-fold decrease) by promoting channel endocytosis."
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"These immunohistochemistry data, together with previous findings that TRIP8b (1a-4) promotes HCN1 surface expression in heterologous cells, suggest that TRIP8b (1a-4) is likely to be a key TRIP8b isoform that promotes the surface expression and efficient targeting of HCN1 to the CA1 distal dendrites."
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"In particular, we suggest that TRIP8b (1a) largely prevents HCN1 misexpression in axons whereas TRIP8b (1a-4) enhances channel surface expression and ensures proper dendritic targeting."
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"In agreement with this notion, TRIP8b isoforms that prevent HCN1 expression have been suggested to be located in adult hippocampal CA1 axons."
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"TRIP8b (1a) also decreases expression of HCN1, although the reduction in current density is ~ 10-fold, significantly less than the effect of TRIP8b (1b-2) or TRIP8b (1b-2-4)."
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"Whereas the SNL deletion only partially inhibited channel downregulation with TRIP8b (1b-2), it fully blocked the effect of TRIP8b (1a) to decrease HCN1 expression."
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"In addition to confirming these in vitro results, we found that downregulation of TRIP8b in vivo inhibited HCN1 membrane expression and Ih in CA1 neurons."
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"Surprisingly, both of these truncated TRIP8b isoforms efficiently downregulated HCN1 surface expression, very similar to the effects of the wild-type isoforms (XREF_FIG)."
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"Given that TRIP8b (1a) downregulates HCN1 surface expression in Xenopus oocytes, our findings suggest that TRIP8b (1a) may act to suppress HCN1 channel misexpression in CA1 neuron axons."
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"TRIP8b (1b-2) overexpression causes a near complete loss of HCN1 surface expression and Ih, in both heterologous cells and hippocampal neurons."
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"Knock-down of TRIP8b impaired the expression of EGFP-HCN1 in CA1 distal dendrites."
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"Differential phosphorylation may also explain why TRIP8b (1a) downregulates HCN1 surface expression in Xenopus oocytes whereas it upregulates HCN1 in a mammalian cell line."
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"The effect of TRIP8b (1a) depends on cellular context, causing a 10-fold decrease in HCN1 surface expression in oocytes while enhancing HCN1 expression in HEK293 cells."
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"Thus, the decreased ability of TRIP8b (1b-2) to abolish HCN1 surface expression seen with truncation of the channel 's SNL tripeptide is rescued upon truncation of the entire non conserved C-terminus of HCN1 (XREF_FIG)."
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"Deletion of the SNL tripeptide caused a selective impairment in the downregulation of HCN1 surface expression by either TRIP8b (1a) or TRIP8b (1b-2)."
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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."
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"Specifically, PEX5L (1b-2–4) reduces HCN1 expression, and (1b-2) results in the sequestering of HCN1 to intracellular puncta in hippocampal CA1 (Lewis et al., 2009; Santoro et al., 2009)."
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"TRIP8b 1a was reported to inhibit the axonal localization of HCN1, and may up- or down-regulate HCN1 surface expression depending on the cell type in which it is expressed."
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"Downregulation of HCN1 surface expression by TRIP8b (1a) in Xenopus oocytes is dependent on the presence of a dileucine adaptor protein trafficking motif in the N-terminal domain of the TRIP8b protein."
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"Of the two remaining hippocampal TRIP8b isoforms, TRIP8b (1a-4) promoted HCN1 surface expression in dendrites whereas TRIP8b (1a) suppressed HCN1 misexpression in axons."
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"Our mutagenesis experiments establish the role of the YXXL and EXXXLL consensus AP binding site motifs, present in exon 2 and exon 5, respectively, in the action of distinct TRIP8b isoforms to decrease the surface expression of HCN1 channels."
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"In contrast, TRIP8b (1a) decreases HCN1 surface expression by 10-fold, and both TRIP8b (1b-2) and TRIP8b (1b-2-4) virtually eliminate channel surface expression."
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"Independently, PEX5L (1a) prevents the axonal expression of HCN1, while PEX5L (1a-4) localizes HCN1 to the distal dendritic layer of CA1 (Lewis et al., 2009; Santoro et al., 2009; Piskorowski et al., 2011)."
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