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First published online March 29, 2004

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Eternal tau points the way

tau is a neuronal microtubule-binding protein whose hyperphosphorylation is associated with formation of neurofibrillary tangles in Alzheimer's disease. tau is thought to promote microtubule assembly, and its phosphorylation by kinases such as GSK3 appears to regulate this activity. Inge Grundke-Iqbal and co-workers now provide evidence that GSK3 regulates another potential function of tau: control of organelle transport (see p. 1653). They show that growth-factor-induced differentiation of PC12 cells leads to phosphorylation of tau by GSK3 and that this is required for anterograde transport of mitochondria. Inhibitors of GSK3 block tau phosphorylation under these conditions and leave mitochondria clustered around the nucleus – transport of other organelles is also blocked. The authors confirm the importance of tau phosphorylation by demonstrating that, in CHO cells transfected with tau, similar mitochondrial clustering is evident in cells when tau is unphosphorylated but not when it is phosphorylated. Since mitochondrial accumulation is a characteristic of Alzheimer's disease, abnormal control of organelle transport by tau could be an important contributing factor. Furthermore, given that GSK3 inhibitors block neurite outgrowth, GSK3/tau-dependent transport pathways could have critical roles in neuronal plasticity.

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Role of tau phosphorylation by glycogen synthase kinase-3ß in the regulation of organelle transport

Yoshitaka Tatebayashi, Niloufar Haque, Yunn-Chyn Tung, Khalid Iqbal, and Inge Grundke-Iqbal
JCS 2004 117: 1653-1663. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?