Secretory Granule Trafficking

Post-Golgi transport of hormone and BDNF vesicles for activity-dependent secretion is important in mediating endocrine function and synaptic plasticity. We examined the role of the cytoplasmic tail of vesicular transmembrane CPE in the transport of POMC/ACTH and BDNF vesicles in the endocrine corticotrophic cell line AtT-20 and hippocampal neurons, respectively. Overexpression of the CPE cytoplasmic tail diminished localization of endogenous POMC and BDNF in the processes of AtT-20 cells and hippocampal neurons. Furthermore, live-cell imaging showed that overexpression of the CPE tail decreased both the velocity and processivity of POMC and BDNF vesicle movement in live primary anterior pituitary cells and hippocampal neurons. Our findings demonstrated that the CPE tail is involved in the processive trafficking of POMC and BDNF vesicles to the plasma membrane for secretion. We then performed pulldown experiments using both AtT-20 cell and mouse brain cytosol in vitro and showed that the cytoplasmic tail of CPE interacted with the motor adaptor protein dynactin and microtubule motors kinesin-2, kinesin-3, and cytoplasmic dynein. Moreover, competition assays using a CPE tail peptide verified specific interaction between the CPE tail and dynactin. Thus, the mechanism for the transport of POMC and BDNF vesicles to the release site for activity-dependent secretion in endocrine cells and neurons requires the interaction of vesicular CPE cytoplasmic tail to anchor these organelles to the microtubule motors.

  • Lou H, Park JJ, Cawley NX, Sarcon A, Sun L, Adams T, Loh YP. Carboxypeptidase E cytoplasmic tail mediates localization of synaptic vesicles to the pre-active zone in hypothalamic pre-synaptic terminals. J Neurochem 2010 Aug;114(3):886-96. Epub 2010 May 18.
  • Park JJ, Cawley NX, Loh YP. A bi-directional carboxypeptidase E-driven transport mechanism controls BDNF vesicle homeostasis in hippocampal neurons. Mol Cell Neurosci 2008;39:63-73.
  • Park JJ, Cawley NX, Loh YP. Carboxypeptidase E cytoplasmic tail-driven vesicle transport is key for activity-dependent secretion of peptide hormones. Mol Endocrinol 2008;22:989-1005.
  • Park JJ, Loh YP. How peptide hormone vesicles are transported to the secretion site for exocytosis. Mol Endocrinol 2008;July 31;22:151-159.
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