SGP-1 increases dendritic and synaptic development dependent on synaptic activity

Neurotrophic factors are a group of secreted proteins which generally regulate neurite outgrowth and synaptic development. SGP-1 has been reported as a neurotrophic factor, though little is known of its effect on neurite outgrowth, and it is unknown whether SGP-1 affects synaptic development. We report here that SGP-1 is distributed in vesicle-like puncta in somas and dendrites of primary neurons in culture, and that SGP-1 is secreted in culture and is taken up by endocytosis in dendrites. Endogenous extracellular activity of SGP-1 promotes dendritic, but not axonal outgrowth. Furthermore, endogenous activity of SGP-1 increases synaptogenesis in hippocampal neurons as determined by measuring the density and size of synaptophysin puncta and by determining the density of dendritic spines, their surface expression of GluR2 and their immunoreactivity for GluR1. The effect of SGP-1 on the amount of postsynaptic receptors in dendritic spines depends on synaptic activity and apparently on activation of MAPK, as inhibition of either of these abolished the affect. Hence, SGP-1 has neurotrophic effects, increasing dendritic growth and promoting synaptic development in an activity-dependent fashion.