Journal article
Tau Potentiates Nerve Growth Factor-induced Mitogen-activated Protein Kinase Signaling and Neurite Initiation without a Requirement for Microtubule Binding
The Journal of biological chemistry, Vol.285(25), pp.19125-19134
06/18/2010
DOI: 10.1074/jbc.M110.105387
PMCID: PMC2885191
PMID: 20375017
Abstract
Microtubule-associated protein Tau is known to bind to and stabilize microtubules, thereby regulating microtubule dynamics. However, recent evidence has indicated that Tau can also interact with various components of intracellular signaling pathways, leading to the possibility that Tau might have a role in signal transduction. Here we provide evidence that during growth factor stimulation of neuronal cells, Tau has functions in advance of the neurite elongation stage. Using Tau-depleted neuronal cell lines, we demonstrate that Tau is required for neurite initiation in a manner that does not involve its microtubule binding function. In addition, we demonstrate that Tau potentiates AP-1 transcription factor activation in response to nerve growth factor (NGF). The effect of Tau on AP-1 activation is mediated through its ability to potentiate the activation of mitogen-activated protein kinase (MAPK), which occurs in response to both NGF and epidermal growth factor. Phosphorylation of Tau at Thr-231 also occurs in response to NGF and is required for Tau to impact on MAPK signaling, whereas the ability of Tau to bind to microtubules is not required. Together, these findings indicate a new functional role for Tau in early neuronal development independent of its established role in microtubule stabilization.
Details
- Title: Subtitle
- Tau Potentiates Nerve Growth Factor-induced Mitogen-activated Protein Kinase Signaling and Neurite Initiation without a Requirement for Microtubule Binding
- Creators
- Chad J Leugers - From theGloria Lee - From the
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.285(25), pp.19125-19134
- DOI
- 10.1074/jbc.M110.105387
- PMID
- 20375017
- PMCID
- PMC2885191
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- American Society for Biochemistry and Molecular Biology; 9650 Rockville Pike, Bethesda, MD 20814, U.S.A
- Grant note
- AG 017753 / National Institutes of Health
- Language
- English
- Date published
- 06/18/2010
- Academic Unit
- Iowa Neuroscience Institute; Immunology; Internal Medicine
- Record Identifier
- 9984065391602771
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