Effettori sfingolipidi

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Effettori sfingolipidi
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Effettori gangliosidi
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Ruolo dei gangliosidi
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Neuraminidasi durante lo sviluppo
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Sintesi GD3 durante lo sviluppo
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Sintesi GM2 durante lo sviluppo
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Gangliosidi durante lo sviluppo
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Knock outs and mutant cells Ectopic GD3 synthase
cDNA expression in neuroblastoma cells resulted
in increased expression of b-series gangliosides
together with neurite outgrowth and cellular
differentiation ( Kojima et al., 1994 Liu et
al., 1997). disruption of the gene encoding
GD3 synthase, a sialyltransferase responsible for
the synthesis of b-series gangliosides, in
embryonic precursor cells stimulated with
differentiating agents produce dendrites and
axons mice with a normal development and a normal
life span disruption of the GM2/GD2 synthase
1,4GalNAc-transferase (EC2.4.1.92) gene blocks
the synthesis of complex gangliosides results
in the expression of only the simple gangliosides
GM3 and GD3 These mutant mice were viable,
with a normal life span and a CNS that was
largely functional only a slight reduction in
the neural conduction velocity (Takamiya et al.,
1996). age-related dysmyelination process
associated with axonal degeneration (Sheikh et
al. 1999) and motor defects (Chiavegatto et al.
2000). CGN from such mice degenerate shen
subjected to elevated K, under conditions that
cause no damage and are beneficial to these cells
in normal mice. These cells seem to have have
lost the capability to regulate calcium since the
depolarizing condition induce progressively
higher calcium levels in the mutant cells
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double mutant GD3S-/- and GalNAcT-/- GM3 as the
major ganglioside. In contrast with the single
mutant mice, it displayed a sudden death
phenotype and was extremely susceptible to
induction of lethal seizures by sound stimulus
(Kawai et al., 2001). neuroblastoma cells
deficient in GM1 synthase exhibit high
vulnerability to agents that increase Ca in
axons. These cells could be rescued from
apoptosis by a permeant form of GM1 but not by
GM1 itself. Glcceramide synthase GlcCer is
essential for development. In the absence of
glycosphingolipid synthesis, embryogenesis is
disrupted by a major apoptotic process
particularly in the ectodermic layer, but also in
other regions of the embryo the ectodermic layer
constitutes the precursor lineage of the
developing nervous system Yamashita et al
1999 differentiation in vitro is still possible
after disruption of the gene encoding
glucosylceramide. However these mutant cells were
severely impaired in their ability to form mature
differentiated tissues in teratomas grown in
mice. Complex gangliosides could be necessary
for the development of the nervous system, and
the lack of complex gangliosides could prevent
cell-cell interactions necessary for the
formation of tissues and organs.
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Mice deficient in UDP-galactose ceramide
galactosyltransferase or sulfotransferase These
mice are still able to form myelin but exhibit
generalized tremor, ataxia, and develop
progressive hind limb paralysis. In place of
GalCer they incorporate a GlcCer with
hydroxylated fatty acid moieties into their
myelin. Stability and function of the myelin
sheath considerably impaired. Generalized tremor,
ataxia, conduction deficits. Kolter et al. 2002
Combinatorial ganglioside biosynthesis J Biol
Chem. 277(29)25859-62.