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.
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9 March 1998
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March 09 1998
Regulation of Neural Cell Adhesion Molecule Polysialylation: Evidence for Nontranscriptional Control and Sensitivity to an Intracellular Pool of Calcium
Juan L. Brusés,
Juan L. Brusés
*Department of Neurosciences and ‡Department of Genetics, Case Western Reserve University, Cleveland, Ohio 44106
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Urs Rutishauser
Urs Rutishauser
*Department of Neurosciences and ‡Department of Genetics, Case Western Reserve University, Cleveland, Ohio 44106
Search for other works by this author on:
Juan L. Brusés
*Department of Neurosciences and ‡Department of Genetics, Case Western Reserve University, Cleveland, Ohio 44106
Urs Rutishauser
*Department of Neurosciences and ‡Department of Genetics, Case Western Reserve University, Cleveland, Ohio 44106
Address correspondence to Dr. Urs Rutishauser, Department of Genetics, Case Western Reserve University, 2109 Adelbert Road, Cleveland, OH 44106. Tel.: (216) 368-2428. Fax: (216) 368-3182. E-mail: [email protected]
The authors acknowledge the excellent technical assistance of Denice Major.
Received:
June 30 1997
Revision Received:
November 24 1997
Online ISSN: 1540-8140
Print ISSN: 0021-9525
1998
J Cell Biol (1998) 140 (5): 1177–1186.
Article history
Received:
June 30 1997
Revision Received:
November 24 1997
Citation
Juan L. Brusés, Urs Rutishauser; Regulation of Neural Cell Adhesion Molecule Polysialylation: Evidence for Nontranscriptional Control and Sensitivity to an Intracellular Pool of Calcium . J Cell Biol 9 March 1998; 140 (5): 1177–1186. doi: https://doi.org/10.1083/jcb.140.5.1177
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