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Astrocyte's clean up job

The Rockefeller University Press
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DOI: 10.1083/jcb.1832iti4
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untitled IN THIS ISSUE • THE JOURNAL OF CELL BIOLOGY 173 Text by Ruth Williams [email protected] not entirely normal: precursor neuroblasts had slightly longer cell cycles and some had bent spindles. Though, neither problem prevented mitosis. The need for APC in some neurons but not others seems to refl ect a requirement for Wnt signaling. As well as its cytoskeletal role, APC is a downstream regulator of Wnt, and while medulla neurons need Wnt for axon growth, the other types of neurons did not. It will be of interest to check whether hippocampal neurons, where the dominant-negative experiments were carried out, are also Wnt responsive. Rusan, N.M., et al. 2008. J. Cell Biol. doi:10.1083/jcb.200807079. Microdomain switching is a bad move for APP Amyloid precursor protein (APP), whose cleavage product, amyloid-� (A�), builds up into fi brous plaques in the brains of Alzheimer’s disease patients, jumps from one specialized membrane microdomain to another to be cleaved, report Sakurai et al. Although there is no defi nitive evidence that A� plaques are the direct cause of Alzheimer’s disease, there is much circumstantial evidence to support this. And working on this hypothesis, scientists are investigating just how the plaques form and what might be done to stop or reverse their formation. APP, a protein of unknown function, is membrane associated and concentrates at the neuronal synapse. Certain factors such as high cellular cholesterol and increased neuronal or synaptic activity are known to drive APP cleavage, and Sakurai and colleagues’ paper pulls these two modes of A� regulation together. APP associates with membrane microdomains high in cholesterols (lipid rafts). These lipid rafts can also contain the enzyme necessary for APP cleavage, BACE. Synaptic activity is known to involve a very different type of membrane microdomain high in an excytosis-promoting factor called syntaxin. Sakurai et al. now show that although APP preferentially associates with

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