Plasma Membrane Ganglioside Sialidase Regulates Axonal Growth and Regeneration in Hippocampal Neurons in Culture

Abstract

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.