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Journal of Neuroscience, Vol 16, 238-252, Copyright © 1996 by Society for Neuroscience
The molecular composition of neuronal microfilaments is spatially and temporally regulated
R Weinberger, G Schevzov, P Jeffrey, K Gordon, M Hill and P Gunning
Developmental Neurobiology Unit, Children's Medical Research Institute, Wentworthville, New South Wales, Australia.
The actin-based microfilament system is thought to play a critical role in
neuronal development. We have determined specific changes in the
composition of microfilaments accompanying neuronal morphogenesis. By using
specific antibodies against the isoforms for tropomyosin (Tm) (Tm- 5 and
TmBr-1/-3) and actin (beta- and gamma-actin), we found that during early
morphogenesis in vivo immature growing axons contain beta- and gamma-actin
and Tm-5. In particular, Tm-5 is exclusively located in the immature axonal
processes relative to the neuronal cell body. In contrast, beta-actin and
Tm-5 are absent in mature, quiescent axons. This developmental loss from
axons is associated with an approximately twofold downregulation of
beta-actin and Tm-5 levels in the brain; gamma-actin levels do not change,
and this molecule is widely distributed throughout neurons during
development. The loss of beta- actin and Tm-5 from axons is accompanied by
a progressive appearance of TmBr-1/-3. This apparent replacement of Tm-5
with TmBr-1/-3 occurs over a 2 d time period during rat embryonic hindbrain
development and is conserved in evolution between birds and mammals. The
loss of Tm-5 from axons involves a redistribution of this molecule to the
cell soma and dendrites. These findings suggest that specialized
microfilament domains are associated with the development and maintenance
of neuronal polarity. We conclude that these Tm isoforms and beta-actin are
subject to specific patterns of segregation associated with axonal
development and neuronal differentiation. This provides a potential
molecular basis for the temporal and spatial specificity of microfilament
function during neuronal differentiation.
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