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Cerebral Cortex Advance Access originally published online on November 21, 2008
Cerebral Cortex 2009 19(7):1666-1677; doi:10.1093/cercor/bhn203
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© The Author 2008. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Major Vault Protein is Expressed along the Nucleus–Neurite Axis and Associates with mRNAs in Cortical Neurons

Constantinos D. Paspalas1, Casey C. Perley2, Deepa V. Venkitaramani2, Susan M. Goebel-Goody2, YongFang Zhang2, Pradeep Kurup2, Joanna H. Mattis2 and Paul J. Lombroso2

1 Division of Neuroanatomy, University of Crete School of Medicine, Heraklion 71003, Greece, 2 Child Study Center, Yale University School of Medicine, New Haven, CT 06520, USA

Address correspondence to Paul J. Lombroso, MD, Child Study Center, Room I-270, Yale University School of Medicine, 230 South Frontage Road, New Haven, CT 06520, USA. Email: Paul.Lombroso{at}yale.edu.

Major Vault Protein (MVP), the main constituent of the vault ribonucleoprotein particle, is highly conserved in eukaryotic cells and upregulated in a variety of tumors. Vaults have been speculated to function as cargo transporters in several cell lines, yet no work to date has characterized the protein in neurons. Here we first describe the cellular and subcellular expression of MVP in primate and rodent cerebral cortex, and in cortical neurons in vitro. In prefrontal, somatosensory and hippocampal cortices, MVP was predominantly expressed in pyramidal neurons. Immunogold labeled free and attached ribosomes, and structures reminiscent of vaults on the rough endoplasmic reticulum and the nuclear envelope. The nucleus was immunoreactive in association with nucleopores. Axons and particularly principal dendrites expressed MVP along individual microtubules, and in pre- and postsynaptic structures. Synapses were not labeled. Colocalization with microtubule-associated protein-2, tubulin, tau, and phalloidin was observed in neurites and growth cones in culture. Immunoprecipitation coupled with reverse transcription PCR showed that MVP associates with mRNAs that are known to be translated in response to synaptic activity. Taken together, our findings provide the first characterization of neuronal MVP along the nucleus–neurite axis and may offer new insights into its possible function(s) in the brain.

Key Words: lung resistance-related protein • microtubule • mRNA transport • nuclear pore • STEP • tPA


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