NEU3 sialidase strictly modulates GM3 levels in skeletal myoblasts C2C12 thus favoring their differentiation and protecting them from apoptosis.

Membrane-bound sialidase NEU3, often referred to as the
“ganglioside sialidase,” has a critical regulatory function on the
sialoglycosphingolipid pattern of the cell membrane, with an
anti-apoptotic function, especially in cancer cells. Although
other sialidases have been shown to be involved in skeletal muscle
differentiation, the role of NEU3 had yet to be disclosed.
Herein we report that NEU3 plays a key role in skeletal muscle
differentiation by strictly modulating the ganglioside content of
adjacent cells, with special regard to GM3. Induced down-regulation
of NEU3 in murine C2C12 myoblasts, even when partial,
totally inhibits their capability to differentiate by increasing the
GM3level above a critical point, which causes epidermal growth
factor receptor inhibition (and ultimately its down-regulation)
and an higher responsiveness of myoblasts to the apoptotic
stimuli.