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Cdk5 and Trio modulate endocrine cell exocytosis

Xiaonan Xin1, Francesco Ferraro, Nils Bäck

  • 1Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA.

Journal of Cell Science
|August 28, 2004
PubMed

Insights

Roscovitine, a cyclin-dependent kinase 5 (Cdk5) inhibitor, reduces pituitary hormone secretion by altering actin cytoskeleton dynamics. This involves Cdk5-mediated activation of Trio, a RhoGEF, impacting secretory granule exocytosis.

Area of Science:

  • Endocrinology
  • Cell Biology
  • Molecular Biology

Background:

  • Pituitary hormone secretion is crucial for endocrine function.
  • The actin cytoskeleton plays a key role in regulating exocytosis and endocytosis.
  • Cyclin-dependent kinase 5 (Cdk5) is implicated in various cellular processes.

Purpose of the Study:

  • To investigate the role of Cdk5 in regulating pituitary hormone secretion.
  • To elucidate the molecular mechanisms by which Cdk5 affects the actin cytoskeleton and exocytosis.
  • To identify potential interactions between Cdk5, Trio, and secretory granule trafficking.

Main Methods:

  • Utilized roscovitine as a Cdk5 inhibitor in pituitary cell models.
  • Performed ultrastructural analysis to examine secretory granule dynamics.
  • Investigated protein-protein interactions between Trio and peptidylglycine alpha-amidating monooxygenase.
  • Assessed the effect of roscovitine on Trio-mediated Rac activation.

Main Results:

  • Roscovitine treatment decreased pituitary hormone secretion.
  • Roscovitine reorganized the cortical actin cytoskeleton, limiting secretory granule-plasma membrane interactions.
  • Trio, a RhoGEF, was found to interact with a secretory granule protein.
  • Cdk5 phosphorylates Trio at consensus sites, inhibiting Trio's ability to activate Rac.

Conclusions:

  • Cdk5-mediated activation of Trio is involved in regulating the cortical actin cytoskeleton.
  • This regulation by Cdk5 and Trio impacts hormone exocytosis and endocytosis in pituitary cells.
  • The findings reveal a novel molecular pathway controlling pituitary hormone release.

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