Age-Related Homeostatic Midchannel Proteolysis of Neuronal L-type Voltage-Gated Ca2+ Channels
文献类型：期刊论文
| 作者 | Michailidis IE1; Abele-Henckels K1; Zhang WK1; Lin BC1; Yu Y1; Geyman LS1; Ehlers MD2; Pnevmatikakis EA3; Yang J[*]1,4 |
| 刊名 | NEURON
 |
| 出版日期 | 2014 |
| 卷号 | 82期号:5页码:1045-1057 |
| 通讯作者 | jy160@columbia.edu |
| 合作状况 | 其它 |
| 英文摘要 | Neural circuitry and brain activity depend critically on proper function of voltage-gated calcium channels (VGCCs), whose activity must be tightly controlled. We show that the main body of the pore-forming alpha(1) subunit of neuronal L-type VGCCs, Ca(v)1.2, is proteolytically cleaved, resulting in Ca(v)1.2 fragment channels that separate but remain on the plasma membrane. This "midchannel'' proteolysis is regulated by channel activity, involves the Ca2+-dependent protease calpain and the ubiquitin-proteasome system, and causes attenuation and biophysical alterations of VGCC currents. Recombinant Ca(v)1.2 fragment channels mimicking the products of midchannel proteolysis do not form active channels on their own but, when properly paired, produce currents with distinct biophysical properties. Midchannel proteolysis increases dramatically with age and can be attenuated with an L-type VGCC blocker in vivo. Midchannel proteolysis represents a novel form of homeostatic negative-feedback processing of VGCCs that could profoundly affect neuronal excitability, neurotransmission, neuroprotection, and calcium signaling in physiological and disease states. |
| 收录类别 | SCI |
| 资助信息 | This work was supported by National Institutes of Health grants NS053494 and NS045383 (to J.Y.), an Established Investigator Award of the American Heart Association (to J.Y.), the Top Talents Program of Yunnan Province, China (to J.Y.), and a postdoctoral fellowship (0625908T) from the American Heart Association (to I.E.M.). M.D.E. is an employee and shareholder of Pfizer. |
| 语种 | 英语 |
| WOS记录号 | WOS:000337359800012 |
| 公开日期 | 2014-10-15 |
| 源URL | [http://159.226.149.42:8088/handle/152453/8039]  |
| 专题 | 昆明动物研究所_离子通道药物研发中心 |
| 作者单位 | 1.Department of Biological Sciences, Columbia University, New York, NY 10027, USA 2.Neuroscience Research Unit, Pfizer Worldwide Research and Development, Cambridge, MA 02139, USA 3.Department of Statistics, Columbia University, New York, NY 10027, USA 4.Ion Channel Research and Drug Development Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China |
| 推荐引用方式 GB/T 7714 | Michailidis IE,Abele-Henckels K,Zhang WK,et al. Age-Related Homeostatic Midchannel Proteolysis of Neuronal L-type Voltage-Gated Ca2+ Channels[J]. NEURON,2014,82(5):1045-1057. |
| APA | Michailidis IE.,Abele-Henckels K.,Zhang WK.,Lin BC.,Yu Y.,...&Yang J[*].(2014).Age-Related Homeostatic Midchannel Proteolysis of Neuronal L-type Voltage-Gated Ca2+ Channels.NEURON,82(5),1045-1057. |
| MLA | Michailidis IE,et al."Age-Related Homeostatic Midchannel Proteolysis of Neuronal L-type Voltage-Gated Ca2+ Channels".NEURON 82.5(2014):1045-1057. |
入库方式： OAI收割
来源：昆明动物研究所
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