The C terminus of the L-type voltage-gated calcium channel Ca(V)1.2 encodes a transcription factor.
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.
Gomez-Ospina
Natalia
N
Department of Neurobiology, Stanford University School of Medicine, 299 Campus Drive, Stanford, CA 94305, USA.
Tsuruta
Fuminori
F
Barreto-Chang
Odmara
O
Hu
Linda
L
Dolmetsch
Ricardo
R
D000595:Amino Acid Sequence; D000818:Animals; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D018929:Cell Culture Techniques; D002460:Cell Line; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology; D003712:Dendrites / Q000378:metabolism; D036681:Fluorescence Recovery After Photobleaching; D017930:Genes, Reporter; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D008156:Luciferases / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D016501:Neurites / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection
D020746:Calcium Channels, L-Type; D014157:Transcription Factors; D008156:Luciferases