Identification of Peptide lv, a novel putative neuropeptide that regulates the expression of L-type voltage-gated calcium channels in photoreceptors.
Identification of Peptide lv, a novel putative neuropeptide that regulates the expression of L-type voltage-gated calcium channels in photoreceptors.
复制标题
DOI：
10.1371/journal.pone.0043091
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ko GY
中科院分区：
文献类型：
--
作者：
Shi L;Ko ML;Abbott LC;Ko GY
神经肽是一种小的蛋白质样信号分子，在调节神经功能如睡眠/觉醒周期、疼痛调节、突触可塑性以及学习和记忆中具有不同的作用。在过去的几十年中，已经开发了许多旨在靶向神经肽、其受体或相关通路的药物。因此，新的神经肽及其功能的发现和表征受到科学研究的极大关注。计算生物信息学与功能分析相结合是解决发现新的生物活性肽的困难的有力工具。在这项研究中，设计了一种新的生物信息学策略来筛选全长人类和小鼠cDNA数据库，以寻找新的肽。其中一种被发现并命名为Lv肽，因为它能够增强视网膜光感受器中的L型电压门控钙通道（L-VGCC）电流。用基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）检测到Lv肽，表明Lv肽是由转染该基因的661 W细胞分泌的。在体外处理与谷胱甘肽S-转移酶（GST）融合肽Lv或合成肽Lv增强L-VGCC通道活动的锥光感受器。在分子水平上，Lv肽刺激视锥细胞cAMP的产生，增强细胞外信号调节激酶（ERK）的磷酸化，增加L-VGCCα1亚基的蛋白表达。因此，Lv肽的生物活性可能在L-VGCC依赖的神经可塑性调节中非常重要。
Neuropeptides are small protein-like signaling molecules with diverse roles in regulating neural functions such as sleep/wake cycles, pain modulation, synaptic plasticity, and learning and memory. Numerous drugs designed to target neuropeptides, their receptors, or relevant pathways have been developed in the past few decades. Hence, the discovery and characterization of new neuropeptides and their functions have received considerable attention from scientific research. Computational bioinformatics coupled with functional assays are powerful tools to address the difficulties in discovering new bioactive peptides. In this study, a new bioinformatic strategy was designed to screen full length human and mouse cDNA databases to search for novel peptides. One was discovered and named peptide Lv because of its ability to enhance L-type voltage-gated calcium channel (L-VGCC) currents in retinal photoreceptors. Using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), peptide Lv was detected in the culture media, which indicated that it was secreted from 661W cells transfected with the gene. In vitro treatments with either glutathione S-transferase (GST) fusion peptide Lv or synthesized peptide Lv enhanced L-VGCC channel activities in cone photoreceptors. At the molecular level, peptide Lv stimulated cAMP production, enhanced phosphorylation of extracellular signal-regulated kinase (ERK), and increased the protein expression of L-VGCCα1 subunits in cone photoreceptors. Therefore, the biological activities of peptide Lv may be very important in the modulation of L-VGCC dependent neural plasticity.
登录
查看更多内容
影响因子：
3
作者：
Choo KH;Tan TW;Ranganathan S
通讯作者：
Ranganathan S
DOI：
10.1111/j.1749-6632.2008.03629.x
发表时间：
2009-01-01
期刊：
TRENDS IN COMPARATIVE ENDOCRINOLOGY AND NEUROBIOLOGY
影响因子：
--
作者：
Lovejoy, David A.;Rotzinger, Susan;Barsyte-Lovejoy, Dalia
通讯作者：
Barsyte-Lovejoy, Dalia
影响因子：
1.9
作者：
GLEASON, E;MOBBS, P;WILSON, M
通讯作者：
WILSON, M
影响因子：
4.7
作者：
Ko, Michael L.;Liu, Yilin;Ko, Gladys Y. -P.
通讯作者：
Ko, Gladys Y. -P.
影响因子：
56.9
作者：
Hummon, Amanda B.;Richmond, Timothy A.;Sweedler, Jonathan V.
通讯作者：
Sweedler, Jonathan V.