Gangliosides Stimulate Calcium Flux in Neuro‐2A Cells and Require Exogenous Calcium for Neuritogenesis

Wu, Gusheng; Vaswani, Kuldeep K.; Lu, Zi‐Hua; Ledeen, Robert W.

doi:10.1111/j.1471-4159.1990.tb04161.x

Cited by 69 publications

(44 citation statements)

References 31 publications

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“…However, GD3s-KO NMJs did not show extra EPP rundown at any condition. This suggests a role for the O-and/or a-series gangliosides in transmitter release at high frequency nerve stimulation, which could be supported by the finding that in particular GM1 ganglioside influences cellular Ca 2+ membrane flux and homeostasis (Wu et al, 2004), including stimulation of Ca 2+ influx in some cell types (Wu et al, 1990). If GM1 would promote Ca 2+ influx at the motor nerve terminal through slowing down Ca 2+ channel inactivation this could explain the extra EPP rundown in the dKO NMJs where GM1 is absent.…”

Section: Increased Rundown Of High-rate Transmitter Release At Dko Sysupporting

confidence: 55%

Neuromuscular synaptic function in mice lacking major subsets of gangliosides

et al. 2008

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Section: Increased Rundown Of High-rate Transmitter Release At Dko Sysupporting

confidence: 55%

Neuromuscular synaptic function in mice lacking major subsets of gangliosides

et al. 2008

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“…In this respect the fine morphological alterations observed in response to B subunit, which were not accompanied by changes in neurofilament protein expression, most probably result from changes in [Ca2 + ]i. Moreover, several recent studies indicate that addition of gangliosides to cerebral neurons (GuCrold et al, 1992) or Neuro-2a cells (Wu et al, 1990) can influence the movement of 45Ca2+ across the plasma membrane and can increase the levels of ionic and membrane-bound Ca2+ in Neuro-2a cells (Spoerri et al, 1990). In the latter instance, such changes in Ca'+ were accompanied by enhanced neuritogenesis and cytoskeletal modifications.…”

Section: Discussionmentioning

confidence: 90%

Interaction of ganglioside GM1 with the B subunit of cholera toxin modulates intracellular free calcium in sensory neurons

Milani

Minozzi

Petrelli

et al. 1992

J of Neuroscience Research

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The B subunit of cholera toxin, which binds specifically to GM1 ganglioside on cell surfaces, has previously been shown to modulate intracellular calcium levels and growth in several cell types. To explore a role for such changes in calcium in the growth regulatory function of cell-associated GM1 in neurons, dissociated neurons from chicken embryonic day 8 dorsal root ganglia were exposed to the B subunit. To enhance sensitivity to B subunit, some neurons were also enriched with added GM1 (100 microM) and then exposed to B subunit. Incubation of naive cultures with 1 microgram/ml of the B subunit was sufficient to produce modest increases in intracellular free calcium above basal levels in a minor percentage of cells for at least 5 min, as measured by fura-2 fluorescence imaging. Pretreatment of the cells with GM1 for 48 hr increased even further the elevations in intracellular free calcium and the percentage of responding neurons observed after B subunit exposure. These increases in intracellular calcium required the presence of external Ca2+, but were not inhibited by calcium channel blockers. Such changes in calcium were accompanied by fine alterations in morphology affecting mostly the branching of neurites and were more pronounced in the presence of GM1. However, the morphological changes did not result in altered neurofilament protein expression. Immunogold electron microscopy using anti-choleragenoid depicted extensive aggregations of immunoreactive gold particles on neuronal surfaces, which were more extensive in cells treated with GM1. The results demonstrate that cell incorporated GM1 may modulate calcium fluxes, perhaps accounting for the growth regulatory functions of GM1 in both neuronal and other cell types.

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“…Possible existence of such mechanism(s) was previously suggested in the demonstration that GM1 and other gangliotetraose gangliosides protected CGN in culture against glutamate toxicity (28) and Neuro-2a cells subjected to Ca 2ϩ ionophore toxicity (17). Calcium modulatory effects of gangliosides have been observed in several other studies, involving both exogenous (29)(30)(31)(32)(33)(34)(35)(36) and endogenous (18,(37)(38)(39)(40)(41)(42)(43)(44) gangliosides. GM1 has been the predominant endogenous ganglioside to be studied from this standpoint, mainly in the context of its plasma membrane locus.…”

Section: Resultsmentioning

confidence: 87%

Cerebellar neurons lacking complex gangliosides degenerate in the presence of depolarizing levels of potassium

Xie

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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Mice engineered to lack GM2͞GD2 synthase (GalNAc-T), with resultant deficit of GM2, GD2, and all gangliotetraose gangliosides, were originally described as showing a relatively normal phenotype with only a slight reduction in nerve conduction. However, a subsequent study showed that similar animals suffer axonal degeneration, myelination defects, and impaired motor coordination. We have examined the behavior of cerebellar granule neurons from these neonatal knockouts in culture and have found evidence of impaired capacity for Ca 2؉ regulation. These cells showed relatively normal behavior when grown in the presence of physiological or moderately elevated K ؉ but gradually degenerated in the presence of high K ؉ . This degeneration in depolarizing medium was accompanied by progressive elevation of intracellular calcium and onset of apoptosis, phenomena not observed with normal cells. No differences were detected in cells from normal vs. heterozygous mice. These findings suggest that neurons from GalNAc-T knockout mice are lacking a calcium regulatory mechanism that is modulated by one or more of the deleted gangliosides, and they support the hypothesis that maintenance of calcium homeostasis is one function of complex gangliosides during, and perhaps subsequent to, neuronal development.GM1 ganglioside ͉ ganglioside-deficient neurons ͉ cerebellar granule neurons ͉ neuritogenesis ͉ intracellular calcium G angliosides are the major sialoglycoconjugates of the vertebrate central nervous system (1, 2) and have been proposed as important determinants in neuronal differentiation (3-5). Early support for this idea came from study of ganglioside storage disease, in which pyramidal neurons of the cerebral cortex were shown to sprout ectopic dendrites from the ''meganeurite'' ganglioside storage area with formation of aberrant synapses (6). The gangliotetraose family, consisting of GM1 and its oligosialo derivatives (GD1a, GD1b, GT1b, GQ1b, etc.), are the predominant forms in the neuron and are biosynthesized by a series of Golgi-localized enzymes that add sugars sequentially to the membrane-anchoring ceramide moiety (7,8). One approach to the study of their mechanistic roles has been development of genetically altered mice or cell lines that overexpress or lack one or more specific ganglioside. Neuro-2a cells overexpressing GD3 and complex gangliosides of the b-series underwent spontaneous neuritogenesis and cholinergic differentiation (9), whereas blockade of GM3 synthase with antisense vector reduced neuritogenesis in cerebellar granule neurons (CGN). † On the other hand, embryonic stem cells deficient in GD3 synthase could be induced to express a complex neurite network, suggesting that b-series gangliosides are not essential for neuronal differentiation of uncommitted precursor cells (10). NG-CR72 cells, mutants of the NG108-15 line deficient in GM1 synthase, were found to respond positively to dendritogenic agents with prolific neurite outgrowth but negatively to axonogenic stimuli with apoptosis (11). The latter effe...

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Gangliosides Stimulate Calcium Flux in Neuro‐2A Cells and Require Exogenous Calcium for Neuritogenesis

Cited by 69 publications

References 31 publications

Neuromuscular synaptic function in mice lacking major subsets of gangliosides

Neuromuscular synaptic function in mice lacking major subsets of gangliosides

Interaction of ganglioside GM1 with the B subunit of cholera toxin modulates intracellular free calcium in sensory neurons

Cerebellar neurons lacking complex gangliosides degenerate in the presence of depolarizing levels of potassium

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