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The Journal of Neuroscience, December 1, 2001, 21(23):9291-9303
A Functional Role for Intra-Axonal Protein Synthesis during
Axonal Regeneration from Adult Sensory Neurons
Jun-Qi
Zheng1, 4,
Theresa K.
Kelly1, 3,
Bieshia
Chang1,
Sergey
Ryazantsev2,
Ayyappan K.
Rajasekaran1,
Kelsey C.
Martin2, 3, and
Jeffery L.
Twiss1, 3
Departments of 1 Pathology and Laboratory Medicine
and 2 Biological Chemistry and 3 Brain
Research Institute, University of California, Los Angeles, California
90095, and 4 Department of Neuroanatomy, Shenyang
Medical College and Medical University of China, Shenyang, China 110001
Although intradendritic protein synthesis has been documented in
adult neurons, the question of whether axons actively synthesize proteins remains controversial. Adult sensory neurons that are conditioned by axonal crush can rapidly extend processes in
vitro by regulating the translation of existing mRNAs (Twiss et
al., 2000). These regenerating processes contain axonal but not
dendritic proteins. Here we show that these axonal processes of adult
sensory neurons cultured after conditioning injury contain ribosomal
proteins, translational initiation factors, and rRNA. Pure
preparations of regenerating axons separated from the DRG cell bodies
can actively synthesize proteins in vitro and contain
ribosome-bound -actin and neurofilament mRNAs. Blocking protein
synthesis in these regenerating sensory axons causes a rapid retraction
of their growth cones when communication with the cell body is blocked
by axotomy or colchicine treatment. These findings indicate that axons
of adult mammalian neurons can synthesize proteins and suggest that,
under some circumstances, intra-axonal translation contributes to
structural integrity of the growth cone in regenerating axons. By
immunofluorescence, translation factors, ribosomal proteins, and rRNA
were also detected in motor axons of ventral spinal roots analyzed
after 7 d in vivo after a peripheral axonal crush
injury. Thus, adult motor neurons are also likely capable of
intra-axonal protein synthesis in vivo after axonal injury.
Key words:
mRNA localization; local protein synthesis; conditioned
neuron; axonal regeneration; nerve regeneration
Copyright © 2001 Society for Neuroscience 0270-6474/01/21239291-13$05.00/0
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