Gangliosides as modulators of dendritogenesis in normal and storage disease-affected pyramidal neurons.
Pyramidal cells initiate the formation of dendritic arbors in a prolific burst of neurite outgrowth during early cortical development. Although morphologically mature pyramidal neurons do not normally sprout additional primary dendrites, the discovery of ectopic dendritogenesis in neuronal storage diseases has revealed that these cells do retain this ability under appropriate stimulation. The capacity for renewal of dendritogenesis has been found to exhibit a species gradient with human > cat, dog, sheep > mouse. A consistent metabolic feature of ectopic dendrite-bearing pyramidal neurons is a heightened intracellular expression of GM2 ganglioside. Elevated expression of this same glycosphingolipid has also been found to correlate with normal dendritogenesis. Immature neurons in developing cat and ferret cortex exhibit high levels of GM2 ganglioside immunoreactivity coincident with normal dendritic sprouting and a similar relationship has now been shown for human cortical development. Ultrastructural studies of all three species revealed GM2 localized to vesicles in a manner consistent with Golgi synthesis and exocytic trafficking to the somatic-dendritic plasmalemma. We propose that GM2 ganglioside functions in glycosphingolipid-enriched microdomains (lipid rafts) in the plasmalemma to promote dendritic initiation through modulation of specific membrane proteins and/or their associated second messenger cascades.
Walkley
S U
SU
Department of Neuroscience, Rose F. Kennedy Center for Research in Mental Retardation and Human Development, Albert Einstein College of Medicine, Bronx, NY 10461, USA. walkley@aecom.yu.edu
Zervas
M
M
Wiseman
S
S
D000818:Animals; D002540:Cerebral Cortex / Q000196:embryology; D003712:Dendrites / Q000502:physiology*; D005314:Embryonic and Fetal Development; D005333:Fetus / Q000378:metabolism; D005678:G(M2) Ganglioside / Q000235:genetics / Q000378:metabolism; D005732:Gangliosides / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009542:Niemann-Pick Diseases / Q000503:physiopathology*; D017966:Pyramidal Cells / Q000502:physiology*; D012016:Reference Values; D012497:Sandhoff Disease / Q000503:physiopathology*; D013661:Tay-Sachs Disease / Q000503:physiopathology*
D005732:Gangliosides; D005678:G(M2) Ganglioside