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The Journal of Neuroscience, November 1, 2001, 21(21):8387-8395
Plasma Membrane Ganglioside Sialidase Regulates Axonal Growth and
Regeneration in Hippocampal Neurons in Culture
Jose Abad
Rodriguez2, 3,
Eugenia
Piddini3,
Takafumi
Hasegawa1,
Taeko
Miyagi1, and
Carlos G.
Dotti2, 3
1 Miyagi Prefectural Cancer Center, Division of
Biochemistry, Medeshima-Shiode, Natori, Miyagi, 981-1293 Japan,
2 Cavalieri Ottolenghi Scientific Institute, Universita
degli Studi di Torino, A. O. San Luigi Gonzaga, Regione Gonzole
10, 10043 Orbassano (TO), Italy, and 3 Cell Biology and
Biophysics Program, European Molecular Biology Laboratory, 69012 Heidelberg, Germany
It has been long recognized that the ganglioside GM1 plays a role
in axonal growth and neuronal differentiation. However, the involvement
of plasma membrane GM1 has been difficult to elucidate. This is
possible now thanks to the recent cloning of plasma membrane ganglioside sialidase (PMGS), the enzyme responsible for the localized hydrolysis of oligosialogangliosides into GM1. In this work we show
that PMGS mRNA and protein levels are high at early developmental stages of the hippocampus and low in adulthood both in
vivo and in vitro. We also demonstrate that
inhibition of PMGS activity blocks axonal elongation, whereas the
increase in PMGS activity dramatically enhances axon growth
and accelerates the polarization of cytoskeletal proteins. Finally, we
show that axotomy close to the cell body in PMGS overexpressing neurons
results in the regrowth of the original axon instead of randomly, as is
the case in control neurons. In all, these results imply that PMGS
activity through the modulation of GM1 surface levels is an important
component of the machinery controlling axonal growth. We hypothesize
that increasing PMGS activity in the adult nervous system may be useful to improve regeneration after nerve damage.
Key words:
plasma membrane sialidase; ganglioside; hippocampal
neuron; axonal growth; axonal regeneration
Copyright © 2001 Society for Neuroscience 0270-6474/01/21218387-09$05.00/0
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