4.5 Article

Subcellular localization and transcription regulatory potency of KCNIP/Calsenilin/DREAM/KChIP proteins in cultured primary cortical neurons do not provide support for their role in CRE-dependent gene expression

Journal

JOURNAL OF NEUROCHEMISTRY
Volume 123, Issue 1, Pages 29-43

Publisher

WILEY
DOI: 10.1111/j.1471-4159.2012.07796.x

Keywords

calcium; neuronal activity; nucleus; subcellular localization; transcription factor

Funding

  1. Estonian Ministry of Education and Research [0140143]
  2. Estonian Science Foundation [8844]
  3. Wellcome Trust [067952]

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KCNIP3/KChIP3 (voltage-dependent K+ channel interacting protein 3), alias Calsenilin and downstream regulatory element antagonist modulator (DREAM), is a multifunctional protein that modulates A-type potassium channels, affects processing of amyloid precursor protein and regulates transcription. KCNIP3 has been described to negatively influence the activity of CREB (cAMP/Ca2+-response element binding protein), an essential factor in neuronal activity-dependent gene expression regulation. However, reports on intracellular localization of KCNIP3 in neurons are diverse and necessitate additional analyses of distribution of KCNIPs in cells to clarify the potential of KCNIP3 to fulfill its functions in different cell compartments. Here, we examined localization of the entire family of highly similar KCNIP proteins in neuronal cells and show that over-expressed isoforms of KCNIP1/KChIP1, KCNIP2/KChIP2, KCNIP3/KChIP3, and KCNIP4/KChIP4 had varied, yet partially overlapping subcellular localization. In addition, although some of the over-expressed KCNIP isoforms localized to the nucleus, endogenous KCNIPs were not detected in nuclei of rat primary cortical neurons. Moreover, we analyzed the role of KCNIP proteins in cAMP/Ca2+-response element (CRE)-dependent transcription by luciferase reporter assay and electrophoretic mobility shift assay and report that our results do not support the role for KCNIPs, including DREAM/Calsenilin/KChIP3, in modulation of CREB-mediated transcription in neurons.

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