Hnrpab regulates neural development and neuron cell survival after glutamate stimulation
- John R. Sinnamon1,2,6,
- Catherine B. Waddell2,3,6,
- Sara Nik4,
- Emily I. Chen4,5 and
- Kevin Czaplinski2,3,7
- 1Program in Neuroscience, Stony Brook University, Stony Brook, New York 11794, USA
- 2Center for Nervous Systems Disorders, Centers for Molecular Medicine, Stony Brook University, Stony Brook, New York 11794, USA
- 3Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York 11794, USA
- 4Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York 11794, USA
- 5Stony Brook University Proteomics Center, Stony Brook University, Stony Brook, New York 11794, USA
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↵6 These authors contributed equally to this work.
Abstract
The molecular mechanisms that govern the timing and fate of neural stem-cell differentiation toward the distinct neural lineages of the nervous system are not well defined. The contribution of post-transcriptional regulation of gene expression to neural stem-cell maintenance and differentiation, in particular, remains inadequately characterized. The RNA-binding protein Hnrpab is highly expressed in developing nervous tissue and in neurogenic regions of the adult brain, but its role in neural development and function is unknown. We raised a mouse that lacks Hnrpab expression to define what role, if any, Hnrpab plays during mouse neural development. We performed a genome-wide quantitative analysis of protein expression within the hippocampus of newborn mice to demonstrate significantly altered gene expression in mice lacking Hnrpab relative to Hnrpab-expressing littermates. The proteins affected suggested an altered pattern of neural development and also unexpectedly indicated altered glutamate signaling. We demonstrate that Hnrpab−/− neural stem and progenitor cells undergo altered differentiation patterns in culture, and mature Hnrpab−/− neurons demonstrate increased sensitivity to glutamate-induced excitotoxicity. We also demonstrate that Hnrpab nucleocytoplasmic distribution in primary neurons is regulated by developmental stage.
Keywords
- RNA-binding proteins
- neural development
- neuron survival
- regulation of gene expression
- mouse genetic knockout
Footnotes
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↵7 Corresponding author.
E-mail Kevin.Czaplinski{at}stonybrook.edu.
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Article published online ahead of print. Article and publication date are at http://www.rnajournal.org/cgi/doi/10.1261/rna.030742.111.
- Received October 4, 2011.
- Accepted November 30, 2011.
- Copyright © 2012 RNA Society