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Trafficking and gating of hyperpolarization-activated cyclic nucleotide-gated channels are regulated by interaction with tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) and cyclic AMP at distinct sites.
J Biol Chem. 2011 Jun 10; 286(23):20823-34.JB

Abstract

Ion channel trafficking and gating are often influenced by interactions with auxiliary subunits. Tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) is an auxiliary subunit for neuronal hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. TRIP8b interacts directly with two distinct sites of HCN channel pore-forming subunits to control channel trafficking and gating. Here we use mutagenesis combined with electrophysiological studies to define and distinguish the functional importance of the HCN/TRIP8b interaction sites. Interaction with the last three amino acids of the HCN1 C terminus governed the effect of TRIP8b on channel trafficking, whereas TRIP8b interaction with the HCN1 cyclic nucleotide binding domain (CNBD) affected trafficking and gating. Biochemical studies revealed that direct interaction between TRIP8b and the HCN1 CNBD was disrupted by cAMP and that TRIP8b binding to the CNBD required an arginine residue also necessary for cAMP binding. In accord, increasing cAMP levels in cells antagonized the up-regulation of HCN1 channels mediated by a TRIP8b construct binding the CNBD exclusively. These data illustrate the distinct roles of the two TRIP8b-HCN interaction domains and suggest that TRIP8b and cAMP may directly compete for binding the HCN CNBD to control HCN channel gating, kinetics, and trafficking.

Authors+Show Affiliations

Davee Department of Neurology and Clinical Neurosciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

21504900

Citation

Han, Ye, et al. "Trafficking and Gating of Hyperpolarization-activated Cyclic Nucleotide-gated Channels Are Regulated By Interaction With Tetratricopeptide Repeat-containing Rab8b-interacting Protein (TRIP8b) and Cyclic AMP at Distinct Sites." The Journal of Biological Chemistry, vol. 286, no. 23, 2011, pp. 20823-34.
Han Y, Noam Y, Lewis AS, et al. Trafficking and gating of hyperpolarization-activated cyclic nucleotide-gated channels are regulated by interaction with tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) and cyclic AMP at distinct sites. J Biol Chem. 2011;286(23):20823-34.
Han, Y., Noam, Y., Lewis, A. S., Gallagher, J. J., Wadman, W. J., Baram, T. Z., & Chetkovich, D. M. (2011). Trafficking and gating of hyperpolarization-activated cyclic nucleotide-gated channels are regulated by interaction with tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) and cyclic AMP at distinct sites. The Journal of Biological Chemistry, 286(23), 20823-34. https://doi.org/10.1074/jbc.M111.236125
Han Y, et al. Trafficking and Gating of Hyperpolarization-activated Cyclic Nucleotide-gated Channels Are Regulated By Interaction With Tetratricopeptide Repeat-containing Rab8b-interacting Protein (TRIP8b) and Cyclic AMP at Distinct Sites. J Biol Chem. 2011 Jun 10;286(23):20823-34. PubMed PMID: 21504900.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Trafficking and gating of hyperpolarization-activated cyclic nucleotide-gated channels are regulated by interaction with tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) and cyclic AMP at distinct sites. AU - Han,Ye, AU - Noam,Yoav, AU - Lewis,Alan S, AU - Gallagher,Johnie J, AU - Wadman,Wytse J, AU - Baram,Tallie Z, AU - Chetkovich,Dane M, Y1 - 2011/04/19/ PY - 2011/4/21/entrez PY - 2011/4/21/pubmed PY - 2011/8/6/medline SP - 20823 EP - 34 JF - The Journal of biological chemistry JO - J Biol Chem VL - 286 IS - 23 N2 - Ion channel trafficking and gating are often influenced by interactions with auxiliary subunits. Tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) is an auxiliary subunit for neuronal hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. TRIP8b interacts directly with two distinct sites of HCN channel pore-forming subunits to control channel trafficking and gating. Here we use mutagenesis combined with electrophysiological studies to define and distinguish the functional importance of the HCN/TRIP8b interaction sites. Interaction with the last three amino acids of the HCN1 C terminus governed the effect of TRIP8b on channel trafficking, whereas TRIP8b interaction with the HCN1 cyclic nucleotide binding domain (CNBD) affected trafficking and gating. Biochemical studies revealed that direct interaction between TRIP8b and the HCN1 CNBD was disrupted by cAMP and that TRIP8b binding to the CNBD required an arginine residue also necessary for cAMP binding. In accord, increasing cAMP levels in cells antagonized the up-regulation of HCN1 channels mediated by a TRIP8b construct binding the CNBD exclusively. These data illustrate the distinct roles of the two TRIP8b-HCN interaction domains and suggest that TRIP8b and cAMP may directly compete for binding the HCN CNBD to control HCN channel gating, kinetics, and trafficking. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/21504900/Trafficking_and_gating_of_hyperpolarization_activated_cyclic_nucleotide_gated_channels_are_regulated_by_interaction_with_tetratricopeptide_repeat_containing_Rab8b_interacting_protein__TRIP8b__and_cyclic_AMP_at_distinct_sites_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(19)49146-1 DB - PRIME DP - Unbound Medicine ER -