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Hyperpolarization-activated, cyclic nucleotide-gated HCN2 cation channel forms a protein assembly with multiple neuronal scaffold proteins in distinct modes of protein-protein interaction.
Genes Cells. 2004 Jul; 9(7):631-40.GC

Abstract

Hyperpolarization-activated cation currents, termed Ih, are non-uniformly distributed along dendritic arbors with current density increasing with increasing distance from the soma. The non-uniform distribution of Ih currents contributes to normalization of location-dependent variability in temporal integration of synaptic input, but the molecular basis for the graded HCN distribution remains to be investigated. The hyperpolarization-activated, cyclic nucleotide-gated cation channels (HCNs) underlie Ih currents and consist of four members (HCN1-HCN4) of the gene family in mammals. In this investigation, we report that HCN2 forms a protein assembly with tamalin, S-SCAM and Mint2 scaffold proteins, using several different approaches including immunoprecipitation of rat brain and heterologously expressing cell extracts and glutathione S-transferase pull-down assays. The PDZ domain of tamalin interacts with HCN2 at both the PDZ-binding motif and the internal carboxy-terminal tail of HCN2, whereas binding of the PDZ domain of S-SCAM occurs at the cyclic nucleotide-binding domain (CNBD) and the CNBD-downstream sequence of the carboxy-terminal tail of HCN2. A protein assembly between HCN2 and Mint2 is formed by the interaction of the munc18-interacting domain of Mint2 with the CNBD-downstream sequence of HCN2. The results demonstrate that HCN2 forms a protein complex with multiple neuronal scaffold proteins in distinct modes of protein-protein interaction.

Authors+Show Affiliations

Department of Biological Sciences, Faculty of Medicine, and Department of Molecular and System Biology, Graduate School of Biostudies, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15265006

Citation

Kimura, Kouji, et al. "Hyperpolarization-activated, Cyclic Nucleotide-gated HCN2 Cation Channel Forms a Protein Assembly With Multiple Neuronal Scaffold Proteins in Distinct Modes of Protein-protein Interaction." Genes to Cells : Devoted to Molecular & Cellular Mechanisms, vol. 9, no. 7, 2004, pp. 631-40.
Kimura K, Kitano J, Nakajima Y, et al. Hyperpolarization-activated, cyclic nucleotide-gated HCN2 cation channel forms a protein assembly with multiple neuronal scaffold proteins in distinct modes of protein-protein interaction. Genes Cells. 2004;9(7):631-40.
Kimura, K., Kitano, J., Nakajima, Y., & Nakanishi, S. (2004). Hyperpolarization-activated, cyclic nucleotide-gated HCN2 cation channel forms a protein assembly with multiple neuronal scaffold proteins in distinct modes of protein-protein interaction. Genes to Cells : Devoted to Molecular & Cellular Mechanisms, 9(7), 631-40.
Kimura K, et al. Hyperpolarization-activated, Cyclic Nucleotide-gated HCN2 Cation Channel Forms a Protein Assembly With Multiple Neuronal Scaffold Proteins in Distinct Modes of Protein-protein Interaction. Genes Cells. 2004;9(7):631-40. PubMed PMID: 15265006.
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TY - JOUR T1 - Hyperpolarization-activated, cyclic nucleotide-gated HCN2 cation channel forms a protein assembly with multiple neuronal scaffold proteins in distinct modes of protein-protein interaction. AU - Kimura,Kouji, AU - Kitano,Jun, AU - Nakajima,Yoshiaki, AU - Nakanishi,Shigetada, PY - 2004/7/22/pubmed PY - 2005/2/24/medline PY - 2004/7/22/entrez SP - 631 EP - 40 JF - Genes to cells : devoted to molecular & cellular mechanisms JO - Genes Cells VL - 9 IS - 7 N2 - Hyperpolarization-activated cation currents, termed Ih, are non-uniformly distributed along dendritic arbors with current density increasing with increasing distance from the soma. The non-uniform distribution of Ih currents contributes to normalization of location-dependent variability in temporal integration of synaptic input, but the molecular basis for the graded HCN distribution remains to be investigated. The hyperpolarization-activated, cyclic nucleotide-gated cation channels (HCNs) underlie Ih currents and consist of four members (HCN1-HCN4) of the gene family in mammals. In this investigation, we report that HCN2 forms a protein assembly with tamalin, S-SCAM and Mint2 scaffold proteins, using several different approaches including immunoprecipitation of rat brain and heterologously expressing cell extracts and glutathione S-transferase pull-down assays. The PDZ domain of tamalin interacts with HCN2 at both the PDZ-binding motif and the internal carboxy-terminal tail of HCN2, whereas binding of the PDZ domain of S-SCAM occurs at the cyclic nucleotide-binding domain (CNBD) and the CNBD-downstream sequence of the carboxy-terminal tail of HCN2. A protein assembly between HCN2 and Mint2 is formed by the interaction of the munc18-interacting domain of Mint2 with the CNBD-downstream sequence of HCN2. The results demonstrate that HCN2 forms a protein complex with multiple neuronal scaffold proteins in distinct modes of protein-protein interaction. SN - 1356-9597 UR - https://www.unboundmedicine.com/medline/citation/15265006/Hyperpolarization_activated_cyclic_nucleotide_gated_HCN2_cation_channel_forms_a_protein_assembly_with_multiple_neuronal_scaffold_proteins_in_distinct_modes_of_protein_protein_interaction_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=1356-9597&date=2004&volume=9&issue=7&spage=631 DB - PRIME DP - Unbound Medicine ER -