期刊
NEURON
卷 90, 期 2, 页码 292-307出版社
CELL PRESS
DOI: 10.1016/j.neuron.2016.03.001
关键词
-
资金
- National Institute of General Medical Sciences (NIGMS) [GM058234]
- National Institute of Neurological Disorders and Stroke (NINDS) [NS24067]
- National Institute of Mental Health (NIMH) [MH071739]
- Simons Foundation
- Mathers Foundation
- Burnett Family Foundation
- Medical Scientist Research Service Award [T32GM007308]
Properly functional CNS circuits depend on inhibitory interneurons that in turn rely upon activity-dependent gene expression for morphological development, connectivity, and excitatory-inhibitory coordination. Despite its importance, excitation-transcription coupling in inhibitory interneurons is poorly understood. We report that PV+ interneurons employ a novel CaMK-dependent pathway to trigger CREB phosphorylation and gene expression. As in excitatory neurons, voltage-gated Ca2+ influx through Ca(V)1 channels triggers CaM nuclear translocation via local Ca2+ signaling. However, PV+ interneurons are distinct in that nuclear signaling is mediated by gamma CaMKI, not gamma CaMKII. CREB phosphorylation also proceeds with slow, sigmoid kinetics, rate-limited by paucity of CaMKIV, protecting against saturation of phospho-CREB in the face of higher firing rates and bigger Ca2+ transients. Our findings support the generality of CaM shuttling to drive nuclear CaMK activity, and they are relevant to disease pathophysiology, insofar as dysfunction of PV+ interneurons and molecules underpinning their excitation-transcription coupling both relate to neuropsychiatric disease.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据