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Journal of Neuroscience, Vol 15, 8259-8267, Copyright © 1995 by Society for Neuroscience
Three distinct axonal transport rates for tau, tubulin, and other microtubule-associated proteins: evidence for dynamic interactions of tau with microtubules in vivo
M Mercken, I Fischer, KS Kosik and RA Nixon
Laboratory for Molecular Neuroscience, McLean Hospital, Belmont, Massachusetts 02178, USA.
Microtubule-associated proteins (MAPs), such as tau, modulate neuronal
shape and process outgrowth by influencing the stability and organization
of microtubules. The dynamic nature of MAP-microtubule interactions in
vivo, however, is poorly understood. Here, we have assessed the stability
of these interactions by investigating the synthesis and axoplasmic
transport of tau in relation to that of tubulin and other MAPs within
retinal ganglion cells of normal adult mice in vivo. Using
immunoprecipitation and Western blot analysis with anti-tau monoclonal and
polyclonal antibodies, we unequivocally identified in optic axons a family
of 50-60 kDa tau isoforms and a second 90-95 KDa tau family, the members of
which were shown to contain the domain of tau encoded by exon 4A. To
measure the rates of translocation of tau proteins in vivo, we injected
mice with 35S- methionine intravitreously and, after 6-30 d, quantitated
the radiolabeled tau isoforms immunoprecipitated from eight consecutive 1.1
mm segments of the nerve and optic tract and separated by electrophoresis.
Linear regression analysis of protein transport along optic axons showed
that the tau isoforms advanced at a rate of 0.2-0.4 mm/d, and other
radiolabeled MAPs, identified by their association with taxol-stabilized
microtubules, moved three- to fivefold more rapidly. By contrast, tubulins
advanced at 0.1-0.2 mm/d, significantly more slowly than tau or other MAPs.
These studies establish that tau is not cotransported with tubulin or
microtubules, indicating that associations of tau with microtubules within
axons are not as stable as previously believed. Our findings also reveal
differences among various MAPs in their interactions with microtubules and
provide evidence that assembly and reorganization of the microtubule
network is an active process even after axons establish connections and
fully mature.
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