S-palmitoylation as a novel regulatory machinery for HCN channels

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K07017
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: National Center of Neurology and Psychiatry (2016-2017); Kurume University (2015)
• Principal Investigator: Itoh Masayuki 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 病態生化学研究部, 科研費研究員 (20442535)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: HCNチャネル / パルミトイル化 / 翻訳後修飾 / KCNHチャネル

Outline of Final Research Achievements

In this study, we found that among hyperpolarization-activated cyclic nucleotide-modulated channel family (HCN1-4), HCN1, HCN2 and HCN4, but not HCN3, are the targets of S-palmitoylation. Further, we identified palmitoylating enzymes that regulate the palmitoylation of HCN2 channel. Multiple Zdhhc-family of palmitoylating enzymes significantly increased the palmitoylation of HCN1 and HCN2 proteins. Especially, 5 Zdhhc proteins (Zdhhc2, Zdhhc3, Zdhhc7, Zdhhc15, and Zdhhc20) augmented the palmitoylation of HCN2 protein approximately over 10-fold of control level. When Zdhhc3 and Zdhhc7 were co-expressed with HCN2 in Xenopus oocytes, these enzymes reduced the current amplitude of HCN2 without affecting transport of HCN2 to plasma membrane. In addition, we found that among KCNH voltage gated K+ channel family, Kv10.1, Kv11.1 and Kv12.2 are novel targets of S-palmitoylation.

Free Research Field

分子生理学