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Calcium‐permeable AMPA receptors containing Q/R‐unedited GluR2 direct human neural progenitor cell differentiation to neurons
Author(s) -
Whitney Nicholas P.,
Peng Hui,
Erdmann Nathan B.,
Tian Changhai,
Monaghan Daniel T.,
Zheng Jialin C.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.07-104661
Subject(s) - ampa receptor , glutamate receptor , microbiology and biotechnology , neurogenesis , calcium , receptor , neural stem cell , calcium imaging , chemistry , calcium signaling , biology , biochemistry , stem cell , organic chemistry
We identify calcium‐permeable α‐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.—Whitney, N. P., Peng, H., Erdmann, N. B., Tian, C., Monaghan, D. T., Zheng, J. C. Calcium‐permeable AMPA receptors containing Q/R‐unedited GluR2 direct human neural progenitor cell differentiation to neurons. FASEB J. 22, 2888‐2900 (2008)