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J. Cell Biol.,
Volume 140, Number 5, March 9, 1998 1177-1186
* Department of Neurosciences and The up- and downregulation of polysialic
acid-neural cell adhesion molecule (PSA-NCAM) expression on motorneurons during development is associated respectively with target innervation and synaptogenesis, and is regulated at the level of PSA enzymatic
biosynthesis involving specific polysialyltransferase activity. The purpose of this study has been to describe
the cellular mechanisms by which that regulation might
occur. It has been found that developmental regulation
of PSA synthesis by ciliary ganglion motorneurons is
not reflected in the levels of polysialyltransferase-1
(PST) or sialyltransferase-X (STX) mRNA. On the
other hand, PSA synthesis in both the ciliary ganglion
and the developing tectum appears to be coupled to the concentration of calcium in intracellular compartments.
This study documents a calcium dependence of polysialyltransferase activity in a cell-free assay over the range
of 0.1-1 mM, and a rapid sensitivity of new PSA synthesis, as measured in a pulse-chase analysis of tissue explants, to calcium ionophore perturbation of intracellular calcium levels. Moreover, the relevant calcium pool
appears to be within a specific intracellular compartment that is sensitive to thapsigargin and does not directly reflect the level of cytosolic calcium. Perturbation of other major second messenger systems, such as
cAMP and protein kinase-dependent pathways, did not
affect polysialylation in the pulse chase analysis. These
results suggest that the shuttling of calcium to different
pools within the cell can result in the rapid regulation of
PSA synthesis in developing tissues.
Department of Genetics, Case Western Reserve University, Cleveland, Ohio 44106
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