Rapid trimming of cell surface polySia by exovesicular sialidase triggers release of preexisting surface neurotrophin [Glycobiology and Extracellular Matrices]
March 6th, 2015 by Sumida, M., Hane, M., Yabe, U., Shimoda, Y., Pearce, O. M. T., Kiso, M., Miyagi, T., Sawada, M., Varki, A., Kitajima, K., Sato, C.
As acidic glycocalyx on primary mouse microglial cells and a mouse microglial cell line Ra2, expression of polysialic acid (polySia/PSA), a polymer of the sialic acid Neu5Ac, was demonstrated. PolySia is known to modulate cell adhesion, migration and localization of neurotrophins mainly on neural cells. PolySia on Ra2 cells disappeared very rapidly after an inflammatory stimulus. Results of knockdown and inhibitor studies indicated that rapid surface clearance of polySia was achieved by secretion of endogenous sialidase Neu1 as an exovesicular component. Neu1-mediated polySia turnover was accompanied by the release of brain-derived neurotrophic factor (BDNF) normally retained by polySia molecules. Introduction of a single oxygen atom change into polySia by exogenous feeding of the non-neural sialic acid Neu5Gc caused resistance to Neu1 induced polySia turnover, and also inhibited the associated release of BDNF. These results indicate the importance of rapid turnover of the polySia glycocalyx by exovesicular sialidases in neurotrophin regulation.