Plasma membrane ganglioside sialidase regulates axonal growth and regeneration in hippocampal neurons in culture

It has been long recognized that the ganglioside GM1 plays a role in axonal growth and neuronal differentiation. However, the involvement of plasma me mbrane GM1 has been difficult to elucidate. This is possible now thanks to the recent cloning of plasma membrane ganglioside sialidase (PMGS), the enz yme responsible for the localized hydrolysis of oligosialogangliosides into GM1. In this work we show that PMGS mRNA and protein levels are high at ea rly developmental stages of the hippocampus and low in adulthood both in vi vo and in vitro. We also demonstrate that inhibition of PMGS activity block s axonal elongation, whereas the increase in PMGS activity dramatically enh ances axon growth and accelerates the polarization of cytoskeletal proteins . Finally, we show that axotomy close to the cell body in PMGS overexpressi ng 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 compo nent of the machinery controlling axonal growth. We hypothesize that increa sing PMGS activity in the adult nervous system may be useful to improve reg eneration after nerve damage.