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First published online 25 August 2004
doi: 10.1242/jcs.01333
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Research Article |
1 Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA
2 Department of Anatomy, Institute of Biomedicine, University of Helsinki, Haartmaninkatu 8, Biomedicum, FI-00014 Helsinki, Finland
* Author for correspondence (e-mail: mains{at}uchc.edu)
Accepted 27 May 2004
Hormone secretion by pituitary cells is decreased by roscovitine, an inhibitor of cyclin-dependent kinase 5 (Cdk5). Roscovitine treatment reorganizes cortical actin and ultrastructural analysis demonstrates that roscovitine limits the ability of secretory granules to approach the plasma membrane or one another. Trio, a multifunctional RhoGEF expressed in pituitary cells, interacts with peptidylglycine
-amidating monooxygenase, a secretory granule membrane protein known to affect the actin cytoskeleton. Roscovitine inhibits the ability of Trio to activate Rac, and peptides corresponding to the Cdk5 consensus sites in Trio are phosphorylated by Cdk5. Together, these data suggest that control of the cortical actin cytoskeleton, long known to modulate hormone exocytosis and subsequent endocytosis, involves Cdk5-mediated activation of Trio.
Key words: GDP/GTP exchange factor (GEF), Cytoskeleton, Actin, Peptidylglycine
-amidating monooxygenase (PAM), RhoGTPase, P21-activated kinase (PAK)
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