Intracellular trafficking and secretion of cerebral dopamine neurotrophic factor in neurosecretory cells.

Cerebral dopamine neurotrophic factor (CDNF) is a novel evolutionary conserved protein which can protect and restore the function of dopaminergic neurons in the rat model of Parkinson's disease, suggesting that CDNF might be beneficial for the treatment of Parkinson's disease. CDNF is widely expressed in neurons in several brain regions including cerebral cortex, hippocampus, substantia nigra, striatum and cerebellum. Human CDNF is glycosylated and secreted from transiently transfected cells; however, the mechanism underlying CDNF secretion is currently unclear. In this study, we found that CDNF could be secreted primarily via the regulated secretion pathway in PC12 cells. The glycosylation of CDNF is not required for its secretion. Moreover, we identified two key subdomains in CDNF which are important for its intracellular localization and secretion. Disrupting helix-1 of CDNF significantly reduces its constitutive and regulated secretion and the helix-1 mutant is retained in the endoplasmic reticulum. Although helix-7 mutation only decreases CDNF regulated secretion and has no effect on its constitutive secretion, which is further supported by the reduction in co-localization of helix-7 mutant with secretory granules. In all, these findings will advance our understanding of the molecular mechanism of CDNF trafficking and secretion.
AuthorsZong-Peng Sun, Lei Gong, Shu-Hong Huang, Zhao Geng, Lei Cheng, Zhe-Yu Chen
JournalJournal of neurochemistry (J Neurochem) Vol. 117 Issue 1 Pg. 121-32 (Apr 2011) ISSN: 1471-4159 [Electronic] England
PMID21235575 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.
Chemical References
  • CDNF protein, human
  • Nerve Growth Factors
  • Animals
  • COS Cells
  • Cells, Cultured
  • Cercopithecus aethiops
  • Endoplasmic Reticulum (metabolism, secretion)
  • Female
  • HEK293 Cells
  • Humans
  • Intracellular Fluid (metabolism, secretion)
  • Nerve Growth Factors (metabolism, secretion)
  • Neurosecretion (physiology)
  • PC12 Cells
  • Pregnancy
  • Protein Transport (physiology)
  • Rats
  • Rats, Sprague-Dawley

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