DOI: 10.1523/jneurosci.3300-04.2004. Regulation of HCN Channel Surface Expression by a Novel C-Terminal Protein-Protein Interaction

Regulation of HCN Channel Surface Expression by a Novel C-Terminal Protein-Protein Interaction

10.1523/jneurosci.3300-04.2004

Crossref journal-article

Society for Neuroscience

The Journal of Neuroscience (393)

Abstract

Hyperpolarization-activated cation currents (Ih) are carried by channels encoded by a family of four genes (HCN1-4) that are differentially expressed within the brain in specific cellular and subcellular compartments. HCN1 shows a high level of expression in apical dendrites of cortical pyramidal neurons and in presynaptic terminals of cerebellar basket cells, structures with a high density ofIh. Expression ofIhis also regulated by neuronal activity. To isolate proteins that may control HCN channel expression or function, we performed yeast two-hybrid screens using the C-terminal cytoplasmic tails of the HCN proteins as bait. We identified a brain-specific protein, which has been previously termed TRIP8b (for TPR-containing Rab8b interacting protein) and PEX5Rp (for Pex5p-related protein), that specifically interacts with all four HCN channels through a conserved sequence in their C-terminal tails.In situhybridization and immunohistochemistry show that TRIP8b and HCN1 are colocalized, particularly within dendritic arbors of hippocampal CA1 and neocortical layer V pyramidal neurons. The dendritic expression of TRIP8b in layer V pyramidal neurons is disrupted after deletion of HCN1 through homologous recombination, demonstrating a keyin vivointeraction between HCN1 and TRIP8b. TRIP8b dramatically alters the trafficking of HCN channels heterologously expressed inXenopusoocytes and human embryonic kidney 293 cells, causing a specific decrease in surface expression of HCN protein andIhdensity, with a pronounced intracellular accumulation of HCN protein that is colocalized in discrete cytoplasmic clusters with TRIP8b. Finally, TRIP8b expression in cultured pyramidal neurons markedly decreases nativeIhdensity. These data suggest a possible role for TRIP8b in regulating HCN channel density in the plasma membrane.

Bibliography

Santoro, B., Wainger, B. J., & Siegelbaum, S. A. (2004). Regulation of HCN Channel Surface Expression by a Novel C-Terminal Protein-Protein Interaction. The Journal of Neuroscience, 24(47), 10750â10762.

Authors 3

Bina Santoro (first)
Brian J. Wainger (additional)
Steven A. Siegelbaum (additional)

References 44 Referenced 174

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Dates

Type	When
Created	20 years, 9 months ago (Nov. 24, 2004, 6:03 p.m.)
Deposited	2 years, 4 months ago (April 13, 2023, 12:28 p.m.)
Indexed	2 days, 13 hours ago (Aug. 29, 2025, 6:27 a.m.)
Issued	20 years, 9 months ago (Nov. 24, 2004)
Published	20 years, 9 months ago (Nov. 24, 2004)
Published Online	20 years, 9 months ago (Nov. 24, 2004)
Published Print	20 years, 9 months ago (Nov. 24, 2004)

Funders 0

None

BibTeX

@article{Santoro_2004, title={Regulation of HCN Channel Surface Expression by a Novel C-Terminal Protein-Protein Interaction}, volume={24}, ISSN={1529-2401}, url={http://dx.doi.org/10.1523/jneurosci.3300-04.2004}, DOI={10.1523/jneurosci.3300-04.2004}, number={47}, journal={The Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Santoro, Bina and Wainger, Brian J. and Siegelbaum, Steven A.}, year={2004}, month=nov, pages={10750–10762} }

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