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Cited by 268

The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.

A Spatial Gradient of Tau Protein Phosphorylation in Nascent Axons

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Mandell, James W., Banker, Gary A.·1996·The Journal of Neuroscience
DOI 10.1523/jneurosci.16-18-05727.1996
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Abstract

Mechanisms underlying axonogenesis remain obscure. Although a large number of proteins eventually become polarized to the axonal domain, in no case does protein compartmentalization occur before or simultaneous with the earliest morphological expression of axonal properties. How then might initially unpolarized proteins, such as the microtubule-associated protein tau, play a role in the microdifferentiation of axons? We hypothesized that tau function could be locally regulated by phosphorylation during the period of axonogenesis. To test this hypothesis, we mapped relative levels of tau phosphorylation within developing cultured hippocampal neurons. This was accomplished using calibrated immunofluorescence ratio measurements employing phosphorylation state-dependent and state-independent antibodies. Tau in the nascent axon is more highly dephosphorylated at the site recognized by the tau-1 antibody than tau in the somatodendritic compartment. The change in phosphorylation state from soma to axon takes the form of a smooth proximo-distal gradient, with tau in the soma, immature dendrites and proximal axon ∼80% phosphorylated at the tau-1 site, and that in the axonal growth cone only 20% phosphorylated. The existence of real spatial differences in tau phosphorylation state was confirmed by in situ phosphatase and kinase treatment. Pervanadate, a tyrosine phosphatase inhibitor, induced rapid tau dephosphorylation within live cells, effectively abolishing the phosphorylation gradient. Thus, the gradient is dynamic and potentially regulatable by upstream signals involving tyrosine phosphorylation. Phosphorylation gradients are likely to be present on many neuronal proteins in addition to tau, and their modulation by transmembrane signals could direct the establishment of polarity.

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Crossref · 10.1523/jneurosci.16-18-05727.1996

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Metadata

Authors
Mandell, J. W., & Banker, G. A.
Venue
The Journal of Neuroscience
Publisher
Society for Neuroscience
Published
1996-09-15
Volume
16
Issue
18
Pages
5727-5740
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
DOI
10.1523/jneurosci.16-18-05727.1996
OpenAlex
W2138070279
Cited by
268
References
8
FWCI
4.44
Type
journal article
Language
en
Open access
hybrid

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