| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| 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.
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