Regulation of HCN Channels by Protein Interactions.
Regulation of HCN Channels by Protein Interactions.
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DOI：
10.3389/fphys.2022.928507
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发表时间：
2022
影响因子：
4
通讯作者：
中科院分区：
文献类型：
--
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超极化激活的环核苷酸敏感 (HCN) 通道是可兴奋细胞阈下膜电位的关键调节因子。四种哺乳动物 HCN 通道异构体 HCN1-HCN4 在全身表达，它们有助于多种生理过程，包括心脏起搏、睡眠-觉醒周期、记忆和躯体感觉。虽然所有 HCN 通道亚型在自身表达时都会产生电流，但一系列新兴的相互作用蛋白质会塑造 HCN 通道兴奋性，从而影响生理相关输出。这些调节蛋白中研究最多的是辅助亚基 TRIP8b，它与 HCN 通道 C 末端的多个位点结合，调节表达并破坏 cAMP 结合，从而微调神经元 HCN 通道兴奋性。对于其他 HCN 通道相互作用伙伴（如细丝蛋白 A、Src 酪氨酸激酶和 MinK 相关肽）的作用机制知之甚少，它们对 HCN 通道门控和表达具有一系列影响。最近，发现肌醇三磷酸受体相关的 cGMP 激酶底物 IRAG1 和 LRMP（也称为 IRAG2）是 HCN4 同工型的特异性调节剂。本综述总结了 HCN 通道的已知蛋白质相互作用伙伴及其作用机制，并确定了我们知识中的差距。
Hyperpolarization-activated, cyclic nucleotide-sensitive (HCN) channels are key regulators of subthreshold membrane potentials in excitable cells. The four mammalian HCN channel isoforms, HCN1-HCN4, are expressed throughout the body, where they contribute to diverse physiological processes including cardiac pacemaking, sleep-wakefulness cycles, memory, and somatic sensation. While all HCN channel isoforms produce currents when expressed by themselves, an emerging list of interacting proteins shape HCN channel excitability to influence the physiologically relevant output. The best studied of these regulatory proteins is the auxiliary subunit, TRIP8b, which binds to multiple sites in the C-terminus of the HCN channels to regulate expression and disrupt cAMP binding to fine-tune neuronal HCN channel excitability. Less is known about the mechanisms of action of other HCN channel interaction partners like filamin A, Src tyrosine kinase, and MinK-related peptides, which have a range of effects on HCN channel gating and expression. More recently, the inositol trisphosphate receptor-associated cGMP-kinase substrates IRAG1 and LRMP (also known as IRAG2), were discovered as specific regulators of the HCN4 isoform. This review summarizes the known protein interaction partners of HCN channels and their mechanisms of action and identifies gaps in our knowledge.
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影响因子：
4.8
作者：
Chen, S;Liang, MC;Ting, AE
通讯作者：
Ting, AE
DOI：
10.1073/pnas.1201997109
发表时间：
2012-05-15
影响因子：
11.1
作者：
Bankston, John R.;Camp, Stacey S.;Zagotta, William N.
通讯作者：
Zagotta, William N.
影响因子：
3.7
作者：
Fisher DW;Luu P;Agarwal N;Kurz JE;Chetkovich DM
通讯作者：
Chetkovich DM
影响因子：
10.8
作者：
Campostrini G;Bonzanni M;Lissoni A;Bazzini C;Milanesi R;Vezzoli E;Francolini M;Baruscotti M;Bucchi A;Rivolta I;Fantini M;Severi S;Cappato R;Crotti L;J Schwartz P;DiFrancesco D;Barbuti A
通讯作者：
Barbuti A
DOI：
10.1523/jneurosci.3994-09.2010
发表时间：
2010-04-21
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Brown JA;Gianino SM;Gutmann DH
通讯作者：
Gutmann DH