The C terminus of the L-type voltage-gated calcium channel Ca(V)1.2 encodes a transcription factor.
Journal - Cell (United States )
Voltage-gated calcium channels play a central role in regulating the electrical and biochemical properties of neurons and muscle cells. One of the ways in which calcium channels regulate long-lasting neuronal properties is by activating signaling pathways that control gene expression, but the mechanisms that link calcium channels to the nucleus are not well understood. We report that a C-terminal fragment of Ca(V)1.2, an L-type voltage-gated calcium channel (LTC), translocates to the nucleus and regulates transcription. We show that this calcium channel associated transcription regulator (CCAT) binds to a nuclear protein, associates with an endogenous promoter, and regulates the expression of a wide variety of endogenous genes important for neuronal signaling and excitability. The nuclear localization of CCAT is regulated both developmentally and by changes in intracellular calcium. These findings provide evidence that voltage-gated calcium channels can directly activate transcription and suggest a mechanism linking voltage-gated channels to the function and differentiation of excitable cells.
|ISSN : ||0092-8674|
|Mesh Heading : ||Amino Acid Sequence Animals Calcium Channels, L-Type Cell Culture Techniques Cell Line Cells, Cultured Cerebral Cortex Dendrites Fluorescence Recovery After Photobleaching Genes, Reporter Humans Ion Channel Gating Luciferases Myocytes, Cardiac Neurites Neurons PC12 Cells Rats Rats, Sprague-Dawley Transcription Factors Transfection chemistry genetics cytology embryology metabolism metabolism metabolism metabolism metabolism|
|Mesh Heading Relevant : ||physiology physiology metabolism|