DPP10 splice variants are localized in distinct neuronal populations and act to differentially regulate the inactivation properties of Kv4-based ion channels
DPP10 splice variants are localized in distinct neuronal populations and act to differentially regulate the inactivation properties of Kv4-based ion channels
复制标题
DOI：
10.1016/j.mcn.2007.03.008
复制
发表时间：
2007-08-01
影响因子：
3.5
通讯作者：
Pfaffinger, Paul J.
中科院分区：
文献类型：
--
作者：
Jerng, Henry H.;Lauver, Aaron D.;Pfaffinger, Paul J.
二肽基肽酶样蛋白（DPLs）和Kv通道相互作用蛋白（KChIPs）加入Kv 4孔形成亚基，形成多蛋白复合物，构成神经元体树突隔室阈下A型电流（I-SA）的基础。在这里，我们的特点的N-末端变体属于DPL二肽基肽酶10（DPP 10）的功能效果和脑分布。在Kv4.2+ KChIP 3 + DPP 10通道复合物中，所有DPP 10变体都加速通道门控动力学;然而，剪接变体DPP 10a产生独特的快速失活动力学，其随着去极化的增加而加速。这种DPP 10a特异性失活在与KChIP 4a和其他DPP 10亚型的共表达研究中占主导地位。实时qRT-PCR和原位杂交分析揭示了大鼠脑中DPP 10变体的差异表达。DPP 10a转录物在皮质中显著表达，而DPP 10 c和DPP 10 d mRNA表现出更弥散的分布。我们的研究结果表明，DPP 10a的基础皮层伊萨的快速失活，和异构体表达的调节可能有助于跨不同的大脑区域的I-SA的可变失活特性。(c)2007爱思唯尔公司All rights reserved.
Dipeptidyl peptidase-like proteins (DPLs) and Kv-channel-interacting proteins (KChIPs) join Kv4 pore-forming subunits to form multiprotein complexes that underlie subthreshold A-type currents (I-SA) in neuronal somatodendritic compartments. Here, we characterize the functional effects and brain distributions of N-terminal variants belonging to the DPL dipeptidyl peptidase 10 (DPP10). In the Kv4.2+KChIP3+DPP10 channel complex, all DPP10 variants accelerate channel gating kinetics; however, the splice variant DPP10a produces uniquely fast inactivation kinetics that accelerates with increasing depolarization. This DPP10a-specific inactivation dominates in co-expression studies with KChIP4a and other DPP10 isoforms. Real-time qRT-PCR and in situ hybridization analyses reveal differential expression of DPP10 variants in rat brain. DPP10a transcripts are prominently expressed in the cortex, whereas DPP10c and DPP10d mRNAs exhibit more diffuse distributions. Our results suggest that DPP10a underlies rapid inactivation of cortical ISA, and the regulation of isoform expression may contribute to the variable inactivation properties of I-SA across different brain regions. (c) 2007 Elsevier Inc. All rights reserved.