The Tetramerization Domain Potentiates Kv4 Channel Function by   Suppressing Closed-State Inactivation

doi:10.1016/j.bpj.2014.07.038

CORC > 北京大学 > 心理与认知科学学院

	The Tetramerization Domain Potentiates Kv4 Channel Function by Suppressing Closed-State Inactivation
	Tang, Yi-Quan ; Zhou, Jing-Heng ; Yang, Fan ; Zheng, Jie ; Wang, Kewei
刊名	biophysical journal
	2014
关键词	U-TYPE INACTIVATION INTRACELLULAR T1-T1 INTERFACE LONG-TERM POTENTIATION GATED K+ CHANNELS POTASSIUM CHANNELS 3-DIMENSIONAL STRUCTURE PYRAMIDAL NEURONS CALCIUM-CHANNELS LIVING CELLS T1 DOMAIN
DOI	10.1016/j.bpj.2014.07.038
英文摘要	A-type Kv4 potassium channels undergo a conformational change toward a nonconductive state at negative membrane potentials, a dynamic process known as pre-open closed states or closed-state inactivation (CSI). CSI causes inhibition of channel activity without the prerequisite of channel opening, thus providing a dynamic regulation of neuronal excitability, dendritic signal integration, and synaptic plasticity at resting. However, the structural determinants underlying Kv4 CSI remain largely unknown. We recently showed that the auxiliary KChIP4a subunit contains an N-terminal Kv4 inhibitory domain (KID) that directly interacts with Kv4.3 channels to enhance CSI. In this study, we utilized the KChIP4a KID to probe key structural elements underlying Kv4 CSI. Using fluorescence resonance energy transfer two-hybrid mapping and bimolecular fluorescence complementation-based screening combined with electrophysiology, we identified the intracellular tetrannerization (T1) domain that functions to suppress CSI and serves as a receptor for the binding of KID. Disrupting the Kv4.3 T1-T1 interaction interface by mutating C110A within the C3H1 Motif of T1 domain facilitated CSI and ablated the KID-mediated enhancement of CSI. Furthermore, replacing the Kv4.3 T1 domain with the T1 domain from Kv1.4 (without the C3H1 motif) or Kv2.1 (with the C3H1 motif) resulted in channels functioning with enhanced or suppressed CSI, respectively. Taken together, our findings reveal a novel (to our knowledge) role of the T1 domain in suppressing Kv4 CSI, and that KChIP4a KID directly interacts with the T1 domain to facilitate Kv4.3 CSI, thus leading to inhibition of channel function.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000341275100010&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Biophysics; SCI(E); PubMed; 0; ARTICLE; wangkw@hsc.plcu.edu.cn; 5; 1090-1104; 107
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/156324]
专题	心理与认知科学学院
推荐引用方式 GB/T 7714	Tang, Yi-Quan,Zhou, Jing-Heng,Yang, Fan,et al. The Tetramerization Domain Potentiates Kv4 Channel Function by Suppressing Closed-State Inactivation[J]. biophysical journal,2014.
APA	Tang, Yi-Quan,Zhou, Jing-Heng,Yang, Fan,Zheng, Jie,&Wang, Kewei.(2014).The Tetramerization Domain Potentiates Kv4 Channel Function by Suppressing Closed-State Inactivation.biophysical journal.
MLA	Tang, Yi-Quan,et al."The Tetramerization Domain Potentiates Kv4 Channel Function by Suppressing Closed-State Inactivation".biophysical journal (2014).