Cdk5 and Trio modulate endocrine cell exocytosis.
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 alpha-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.
Xin
Xiaonan
X
Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA.
Ferraro
Francesco
F
Bäck
Nils
N
Eipper
Betty A
BA
Mains
Richard E
RE
D000199:Actins / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077546:Roscovitine; D020798:Two-Hybrid System Techniques; D020744:rac GTP-Binding Proteins / Q000378:metabolism
D000199:Actins; D020662:Guanine Nucleotide Exchange Factors; D009419:Nerve Tissue Proteins; D047428:Protein Kinase Inhibitors; D011687:Purines; C500736:Trio protein, rat; D000077546:Roscovitine; D051360:Cyclin-Dependent Kinase 5; C495907:Cdk5 protein, rat; D018844:Cyclin-Dependent Kinases; D020744:rac GTP-Binding Proteins