Cell biology of the neuron: The long and short of GluR2 expression


It is easy to think of amyloid precursor protein (APP) as ‘one of the bad guys’, because of the involvement of its derivative β-amyloid in Alzheimer’s disease pathogenesis. Yet the abundance of APP in normal tissues, including the brain, implies that it has an important physiological role. Reporting in Development, Caillé and colleagues present new evidence that sAPP — a soluble secreted form of APP — is involved in the maintenance of the neural progenitor cell pool in the adult brain. It was previously shown that sAPP enhances the proliferation of embryonic neural precursor cells in vitro, and Caillé et al. asked whether it has a similar function in the subventricular zone (SVZ) of the adult mouse brain. By probing sections of brain tissue with an antibody-tagged sAPP molecule, they showed that the SVZ contains binding sites for sAPP. Moreover, they found that sAPP binds to a population of cells that proliferate in response to epidermal growth factor (EGF). These EGF-responsive cells were recently identified as type C cells — a subpopulation of stem cells that divide rapidly to amplify the SVZ neural progenitor pool. To investigate the actions of sAPP and its functional relationship with EGF, the authors analysed EGF-responsive SVZ cells that were growing as aggregates, or neurospheres, in culture. They showed that EGF stimulates secretion of sAPP from these neurospheres. If sAPP was sequestered in the tissue culture medium using antibodies, there was a marked decrease in neurosphere expansion, indicating that sAPP is required for EGF-induced proliferation of SVZ cells. However, sAPP could not stimulate neurosphere cell division on its own, indicating that it acts as a co-factor of EGF. Next, Caillé et al. examined the effects of sAPP on neural progenitor proliferation in the mouse brain in vivo. They showed that an infusion of sAPP into the lateral ventricle caused an increase in the size of the EGF-responsive neural precursor pool in the SVZ. Conversely, when they blocked the activity of α-secretase — the enzyme that releases sAPP from APP — they A

DOI: 10.1038/nrn1416

Cite this paper

@article{Craven2004CellBO, title={Cell biology of the neuron: The long and short of GluR2 expression}, author={Rebecca Craven}, journal={Nature Reviews Neuroscience}, year={2004}, volume={5}, pages={434-434} }