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Nicotine-induced Ca2+-myristoyl Switch of Neuronal Ca2+ Sensor VILIP-1 in Hippocampal Neurons: A Possible Crosstalk Mechanism for Nicotinic Receptors

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Abstract

Visinin-like protein (VILIP-1) belongs to the neuronal Ca2+ sensor family of EF-hand Ca2+-binding proteins that regulate a variety of Ca2+-dependent signal transduction processes in neurons. It is an interaction partner of α4β2 nicotinic acetylcholine receptor (nAChR) and increases surface expression level and agonist sensitivity of the receptor in oocytes. Nicotine stimulation of nicotinic receptors has been reported to lead to an increase in intracellular Ca2+ concentration by Ca2+-permeable nAChRs, which in turn might lead to activation of VILIP-1, by a mechanism described as the Ca2+-myristoyl switch. It has been postulated that this will lead to co-localization of the proteins at cell membranes, where VILIP-1 can influence functional activity of α4-containing nAChRs.

In order to test this hypothesis we have investigated whether a nicotine-induced and reversible Ca2+-myristoyl switch of VILIP-1 exists in primary hippocampal neurons and whether pharmacological agents, such as antagonist specific for distinct nAChRs, can interfere with the Ca2+-dependent membrane localization of VILIP-1.

Here we report, that only α7- but not α4-containing nAChRs are able to elicit a Ca2+-dependent and reversible membrane-translocation of VILIP-1 in interneurons as revealed by employing the specific receptor antagonists dihydro-beta-erythroidine and methylallylaconitine.

The nAChRs are associated with processes of synaptic plasticity in hippocampal neurons and they have been implicated in the pathology of CNS disorders, including Alzheimer’s disease and schizophrenia. VILIP-1 might provide a novel functional crosstalk between α4- and α7-containing nAChRs.

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Acknowledgments

This work was conducted within the framework of the national priority program (Schwerpunktprogram) SPP1226 Nicotine: Molecular and physiological mechanisms in the central nervous system (www.nicotine-research.com) funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG, grant Br1579/9-1) and DFG grant (Br1579/8-1) to K·H.B, and from the National Institutes of Health (DA 019675) and NARSAD (to R.A).

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Authors and Affiliations

  1. Signal Transduction Research Group, Neuroscience Research Center, Charité Universitaetsmedizin Berlin, Berlin, Germany

    CongJian Zhao & Karl-Heinz Braunewell

  2. Department of Pharmacology, The Ohio State University College of Medicine, Columbus, OH, USA

    Rene Anand

  3. Institute for Neurophysiology, Charité Universitaetsmedizin Berlin, Berlin, Germany

    Karl-Heinz Braunewell

  4. Molecular and Cellular Neuroscience Laboratory, Department Biochemistry and Molecular Biology, Southern Research Institute, 2000 Ninth Avenue South, Birmingham, AL, 35205, USA

    Karl-Heinz Braunewell

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  1. CongJian Zhao
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Correspondence to Karl-Heinz Braunewell.

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Zhao, C., Anand, R. & Braunewell, KH. Nicotine-induced Ca2+-myristoyl Switch of Neuronal Ca2+ Sensor VILIP-1 in Hippocampal Neurons: A Possible Crosstalk Mechanism for Nicotinic Receptors. Cell Mol Neurobiol 29, 273–286 (2009). https://doi.org/10.1007/s10571-008-9320-z

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