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PMID: 18403631 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Calcium-permeable AMPA receptors containing Q/R-unedited GluR2 direct human neural progenitor cell differentiation to neurons.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology ·Vol. 22 ·No. 8 ·2008-08-00 ·Pages 2888-900

Whitney NP, Peng H, Erdmann NB, Tian C, Monaghan DT, Zheng JC

Abstract

We identify calcium-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors on human neural progenitor cells (NPCs) and present a physiological role in neurogenesis. RNA editing of the GluR2 subunit at the Q/R site is responsible for making most AMPA receptors impermeable to calcium. Because a single-point mutation could eliminate the need for editing at the Q/R site and Q/R-unedited GluR2 exists during embryogenesis, the Q/R-unedited GluR2 subunit presumably has some important actions early in development. Using calcium imaging, we found that NPCs contain calcium-permeable AMPA receptors, whereas NPCs differentiated to neurons and astrocytes express calcium-impermeable AMPA receptors. We utilized reverse-transcription polymerase chain reaction and BbvI digestion to demonstrate that NPCs contain Q/R-unedited GluR2, and differentiated cells contain Q/R-edited GluR2 subunits. This is consistent with the observation that the nuclear enzyme responsible for Q/R-editing, adenosine deaminase (ADAR2), is increased during differentiation. Activation of calcium-permeable AMPA receptors induces NPCs to differentiate to the neuronal lineage and increases dendritic arbor formation in NPCs differentiated to neurons. AMPA-induced differentiation of NPCs to neurons is abrogated by overexpression of ADAR2 in NPCs. This elucidates the role of AMPA receptors as inductors of neurogenesis and provides a possible explanation for why the Q/R editing process exists.

MeSH Terms
Adenosine Deaminase/genetics,metabolism Astrocytes/cytology,metabolism Base Sequence Calcium/metabolism Cell Differentiation/drug effects Cell Membrane Permeability Cells, Cultured DNA Primers/genetics Dendrites/ultrastructure Embryonic Stem Cells/cytology,drug effects,metabolism Gene Expression Glutamic Acid/pharmacology Humans Neurons/cytology,drug effects,metabolism RNA Editing RNA, Messenger/genetics,metabolism RNA-Binding Proteins Receptors, AMPA/genetics,metabolism
Chemicals
DNA Primers RNA, Messenger RNA-Binding Proteins Receptors, AMPA Glutamic Acid ADARB1 protein, human Adenosine Deaminase glutamate receptor ionotropic, AMPA 2 Calcium
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Whitney Nicholas P
Laboratory of Neurotoxicology, University of Nebraska Medical Center, 985800 Nebraska Medical Center, Omaha, NE 68198, USA.
Peng Hui
Erdmann Nathan B
Tian Changhai
Monaghan Daniel T
Zheng Jialin C
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Article Info
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Abbr.
FASEB J
ISSN
1530-6860
DOI
10.1096/fj.07-104661
Published
2008-08-00
Epub
2008-00-10
Pages
2888-900
Language
English
Region
United States
NLM ID
8804484
PMCID
PMC2493446
Subset
IM
Grants
NINDS NIH HHS · R01 NS 41858 · United States
NINDS NIH HHS · P01 NS043985 · United States
NINDS NIH HHS · R01 NS041858 · United States
NCRR NIH HHS · P20 RR15635 · United States
NCRR NIH HHS · P20 RR015635 · United States
External Links
PubMed source DOI: 10.1096/fj.07-104661 PMC Full Text View journal details
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